Evaluation of Three Methods of Treatment of Hypersplenism...Hypersplenism is characterized by cytopenia, splenomegaly, increased or normal medullar cellularity, and elevated turnover

iMedPub Journalswww.imedpub.com

Journal of Hospital & Medical Management ISSN 2471-9781

2017Vol.3 No.3:21

1© Under License of Creative Commons Attribution 3.0 License | This article is available in: http://hospital-medical-management.imedpub.com/archive.php

Review Article

DOI: 10.4172/2471-9781.100040

Hammad A*1, Abdel Modaber AM1 and Aliyev V2

1 General Surgery Department, Faculty of Medicine, Mansoura University, Egypt2 General Surgery Department, Emsey

Hospital, İstanbul, Turkey

*Corresponding author: Hammad A

[email protected]

General Surgery Department, Faculty of Medicine, Mansoura University, El Gomhouria St, Mansoura, Dakahlia Governorate 35516, Egypt.

Tel: +20 50 2383781

Citation: Hammad A, Abdel Modaber AM, Aliyev V (2017) Evaluation of Three Methods of Treatment of Hypersplenism. J Hosp Med Manage Vol.3 No.3:21

Evaluation of Three Methods of Treatment of Hypersplenism

AbstractThis study was conducted for evaluation of safety, efficacy and complications of using open splenectomy, splenic artery embolization and laparoscopic splenectomy in treating hypersplenism. The study included 35 patients; 20 males and 15 females with mean age of 46 years with hypersplenism. They were admitted at General Surgery Department, Zagazig University over a period between 2013 and 2015. All patients were subjected to thorough history taking, clinical examination, full laboratory investigations, upper gastrointestinal endoscopy, abdominal ultrasound and duplex scan. They were divided into three groups according to line of management. Group I patients were treated by open splenectomy, while group II patients were treated by Partial splenic artery embolization (PSE) and group III patients were treated by laparoscopic splenectomy. In group I, there was one mortality recorded due to uncontrollable intraoperative bleeding and also one mortality in group III due to gastric fisula, while in group II, no mortality was recorded. PSE was a significant, rapid procedure and had shorter hospital stay and no blood transfusion was needed, while group I and group III had longer hospital stay and need blood transfusion. Marked improvement in platelet and leucocyte counts occurred in group I and group III and remained at normal level during follow-up period. In group II, there was improvement of platelets and leucocytes but not marked as groups I and III and there was a slight decrease in platelet count during follow-up period but not decrease as pre-embolization period. Liver function tests were normal during follow-up period in most cases in groups I and III as most cases were Child A. In group II patients, liver function tests were elevated during follow up as most cases were Child B. In group I, 13 patients had postoperative fever (> 39°C) due to chest and wound infection, one patient had asymptomatic portal vein thrombosis and one patient had incisional hernia treated by hernioplasty and one patient had splenic bed collection was treated by Apocath insertion and one patient developed ascites during follow-up period treated by liver support. Pancreatitis and OPSI did not occur in our patients. In group II, 11 patients had postoperative fever (>38°C) treated by NSAID, three patients had ascites and one patient developed splenic abscess was treated by splenectomy with good outcome, and one patient had recurrence post-embolization. In group III, three patients were converted to open splenectomy due to intraoperative bleeding and lack of experience of the surgeon and one patient was completed till the end of operation laparoscopically, one patient died during follow up due to gastric fistula. Our study shows that laparoscopic splenectomy is a good operation for ITP patients, but still needs more training, more experience and more cases to improve the results.

Keywords: Spleen; Hypersplenism

Received: November 07, 2017; Accepted: December 04, 2017; Published: December 25, 2017

2 This article is available in: http://hospital-medical-management.imedpub.com/archive.php

ARCHIVOS DE MEDICINAISSN 1698-9465

2017Vol.3 No.3:21


IntroductionThe spleen is involved in producing protective humoral antibodies, the production and maturation of B and T cells and plasma cells, removal of unwanted particulate matter (e.g. Bacteria) and it also acts as a reservoir for blood cells, especially white cells and platelets. When the spleen is palpable it has usually reached at least twice its normal size [1].

Hypersplenism is characterized by cytopenia, splenomegaly, increased or normal medullar cellularity, and elevated turnover of the involved cellular line. The causes of hypersplenism include an increased demand for splenic function, infiltrative diseases of the spleen, and passive splenic congestion due to portal hypertension. Hypersplenism resulting from portal hypertension associated with congestive splenomegaly is frequently due to liver cirrhosis [2].

The criteria to diagnose hypersplenism include splenomegaly, a peripheral blood picture of anemia, neutropenia, and thrombocytopenia (either singly or in combination), a cellular bone marrow, and significant improvement in peripheral blood picture following splenectomy [3].

No universally accepted therapy has been established for hypersplenism. Blood transfusions may be required the usual treatment for hypersplenism is open or laparoscopic splenectomy (to control or stage the disease e.g. hereditary spherocytosis and Hodgkin's disease) or splenic artery embolization. However, it may cause a high morbidity and mortality rate. Tran’s catheter ablation of splenic parenchyma is an alternative treatment modality [4].

Laparoscopic Splenectomy (LS) has become the gold standard for the removal of normal-to-moderately enlarged spleens in benign conditions. Compared with Open Splenectomy (OS), fewer postsurgical complications and better postoperative recovery were observed, but it is contraindicated for hypersplenism owing to technical difficulties associated with splenomegaly, well-developed collateral circulation, and increased risk of bleeding. With the improvements of laparoscopic technique, the concept is changing [5].

Splenic artery embolization, first performed by Maddison [6], has been used in patients with hypersplenism, hematologic disorders, and splenic trauma. However, its clinical usefulness has been reduced because of its complications such as splenic abscess formation, splenic rupture, and septicemia encountered after embolization with Gelfoam cubes [7].

Yoshida et al. [8] recommended that embolization of intrasplenic arterial branches of the splenic artery produces infarction of one-third to one-half the spleen to increase platelet counts in patients with platelet counts under 50,000/mm3. Embolization of the proximal splenic artery or the splenic artery at the hilum of the spleen maintains platelet levels in patients with platelet counts over 50,000/mm3.

Abdallah et al. [9] have advocated that splenic artery embolization be performed only as a prelude to open or laparoscopic

splenectomy to avoid serious post embolization complications or in patients for whom surgical splenectomy represents a considerable risk.

The aim of the work is to evaluate the outcome of different methods of treatment of hypersplenism which include open and laproscopic splenectomy and splenic artery embolization and to evaluate their complications.

Patients and MethodsThis current study is a prospective randomized study to determine the safety, efficacy and complications of using open splenectomy, partial splenic embolization, and laparoscopic splenectomy in treating hypersplenism.

Patient populationThis study included 35 patients (20 males and 15 females). Their ages ranged from 23 to 70 years with the mean age of 46 years.

All patients with hypersplenism were admitted at General surgery Department, Zagazig University Hospitals over a period between 2013 and 2015.

Patients were randomly classified into three groups:

• Group (I) treated by spelenctomy with or without devascularization and ligation of left gastric vessels according to presence or absence of bleeding esophageal varices.

• Group (II) treated by percutaneous transcatheter partial splenic embolization.

• Group (III) treated by laparoscopic splenectomy.

All patients in this study had a reduction in one or more of the cellular element of blood with normocellular or hypercellular bone marrow.

Exclusion criteria• Patients with hypo cellular or infiltrative bone marrow

disease.

• Patients with ischemic heart disease.

• Medically unstable patients with multisystem dysfunction.

• Known allergy to contrast medium.

• Psychiatric illnesses and substance abuse.

Patient's evaluationAll patients were subjected to the following:

I. Detailed history taking including personal history, history of present illness, past history of jaundice, bleeding tendency or episodes of hematemesis and/or melena.

II. Complete clinical examination to evaluate the state of spleen, liver, ascites, collaterals, ecchymosis, and manifestations of liver cell failure.

III. Laboratory investigations including:

3© Under License of Creative Commons Attribution 3.0 License


2017Vol.3 No.3:21


• Complete blood picture (Hb, RBCs, WBCs and platelets).

• Complete liver function tests (SGOT, SGPT, albumin and bilirubin).

• Serum creatinine.

• Fasting and postprandial blood sugar.

• Prothrombin concentration and International Normalization Ratio (INR).

• HBsAg, anti-HCV and anti-HIV.

• Bone marrow aspiration and biopsy to prove or refute hyperplenism.

IV. Upper GIT endoscopy. Fiberoptic endoscopic examination was done to diagnose the presence or absence of esophageal and fundal varices and to detect any other associated lesions.

V. Radiology including:

a. Abdominal ultrasonography to examine the size and echopattern of liver, size of spleen and presence or absence of ascites.

b. Color-coded duplex scanning of the portal circulation to verify patency of portal vein, the direction of flow and flow velocity.

Child-Pugh severity grading system was used to assess all patients.

Group I (splenectomy with or without devascularization) (20 patients)Preoperative preparation

1) Informed consent was obtained from all patients after a full and frank discussion of the benefits and risks of the operation.

2) Patients fasting for at least 8 hours before the operation.

3) Intravenous antibiotic wsa given with induction of anesthesia (2 gm cephradine) and for 3 days postoperatively (1 gm cephradine/12 hours).

4) Abdomen shaved from nipples to mid-thigh and a nasogastric tube passed.

5) At least 2 units of blood with cross-matching must be present at the time of operation.

6) Risk of post-spelenctomy sepsis necessitates prophylactic immunization against streptococcus pneumonia. Pneumococcal vaccination taken 7 days before splenectomy.

Operation• Splenic exploration and assessment of mobility.

• Ligation of the splenic artery in the lesser sac.

• Mobilization of the spleen.

• Division of the short gastric vessels.

• Division of the splenocolic ligament.

• Ligation of the hilar vessels.

• Searching for accessory spleens and subsequent closure.

Postoperative care1) Intravenous infusion of crystalloids to maintain hydration

is usually necessary for about 48 hours and nasogastric suction discontinued after 24 hours unless aspirate remains high.

2) CBC was done daily during hospital stay.

3) Serum amylase was measured 24 hours postoperatively to exclude pancreatitis.

4) Suction drainage from splenic bed was removed on the second postoperative day.

5) Abdominal US and duplex scan were done on the seventh postoperative day to exclude portal vein thrombosis.

6) Wound sutures were removed 7-10 days postoperatively.

7) Patients were adviced to seek medical advice promptly whenever infection is contracted or seems likely.

Group II (partial splenic embolization) (11 patients)Preparation

a) Informed consent was obtained from all patients after a full and frank discussion of the benefits and risks of the procedure.

b) Patients fasting for at least 8 hours before the procedure and enema were done for all patients in the night before embolization.

c) Intravenous line was established and the patients were well hydrated (because of the potential need for large volume of contrast medium).

d) Antibiotics were used one day preoperatively (1 gm cefoperazone/12 hours) and for 5 days after embolization.

e) The intended puncture site (inguinal region) was shaved immediately before the procedure in the radiology unit, in order to reduce the superficial skin irritation with infection caused by shaving.

Embolization techniques- We followed strict sterile technique during the procedure. All

personnel involved in the embolization wore facemasks and caps in addition to the usual sterile gowns and gloves.

- On the angiography table, patients were asked to lie in a supine position, in a comfortable position that can be tolerated for the duration of the procedure. A sterile puncture site preparation (iodinated scrub) was done. Local anesthesia was infused with 10 ml of 2% xylocaine (lidocaine hydrochloride 20 mg/ml) at the site of puncture.

- The entry site is the site where right common femoral artery



2017Vol.3 No.3:21


pulsation was well felt by palpating the skin over the femoral artery in the groin.

- Small skin incision was done; the puncture was done using a Seldinger needle (18 gauge=0.042 inch) angled parallel to the course of the femoral artery; about 45 degrees with the skin. Once a good pulsatile blood returned through the needle, the stylet was removed and a terumo straight guide wire (0.032 inch) was gently advanced up to lower abdominal aorta under fluoroscopic guidance. The needle was removed, a 5 or 6 F sheaths was inserted along the guide wire and fixed in place. The position of the sheath within the femoral artery ewas confirmed by saline injection and blood aspiration.

- Four or five cobra head catheter was advanced along the guide wire through the femoral artery into the abdominal aorta, selective catheterization of the celiac axis and splenic artery was performed.

- A preliminary splenic angiogram was obtained to determine the configuration of splenic artery and locatin of its pancreatic branches. The catheter was then advanced forward, if possible, so that its tip lays distal to the last major pancreatic branch to minimize the risk of pancreatitis, or better in one of the polar branches of the splenic artery.

- After being sure that the catheter within the splenic artery or one of its polar branches using fluoroscopic guidance, the guidewire was removed and the embolic agent was gently injected through the catheter using free flow technique. The injection of embolic material was done very slowly to avoid its reflux.

- The embolic agent used in this study was gel foam.

- During embolization, small amount of contrast material was periodically injected through the catheter to monitor the flow distribution within the spleen. After completing embolization splenic angiography was performed to confirm reduction of approximately 50% of splenic blood flow.

- After that, the catheter was irrigated by saline and removed. Compression was done over the site of puncture for about 10-15 minutes. Then, the site of puncture was covered and patients were asked to extend their legs and maintain bed rest for the rest of the day of procedure.

- After the procedure, the site of puncture was observed every 15 minutes for 4 hours then every 30 minutes for 4 hours then every 4 hours for 16 hours to detect bleeding or hematoma as early as possible.

Post-embolization period1) Bed rest one day after the procedure.

2) Observation of puncture site and vital signs.

3) High fluid intake is important.

4) IV antibiotic (1 gm coefoperazone 1 12 hours) was continued for 5 days to decrease the risk of splenic abscess.

5) Analgesia was given (in the form of non-steroidal anti-inflammatory) not only for the patient's comfort but also to reduce the risk of complications, as abdominal pain may impair breathing motion, which may in turn leads to atelectasis and pneumonia.

6) Serum amylase measurement was done 24 hours after embolization to exclude hyperamylasemia and/or pancreatitis.

7) Chest radiographs were obtained as indicated to exclude the possibility of pneumonia or pleural effusion.

8) Abdominal ultrasound was done in all patients to look for evidence of splenic abscess two weeks after the procedure.

Group III (laparoscopic splenectomy) (4 patients)Positioning of the patient and room setting: This is achieved by placing the patient in the right lateral decubitus position and to increase the distance between the lower margin of the thoracic cage and the iliac crest, the operating table must be flexed and the kidney bolster elevated. Some surgeons prefer a slight tilt of the patient backward, and place the abdominal side of the patient nearer to the table edge. Room setting is: Surgeon and camera operator stand on the right of the patient with the operator to the right of the surgeon. In consistence with coaxial alignment, the monitor is to the left of the patient. The mayo''s stand near the feet.

Insertion of trocars: Four 12 mm trocars usually introduced in the subcostal margin. By this, the telescope, the clipper, and the linear stapler interchanged as needed taking into consideration a good distance between them to have good working angles. Some surgeons prefer a slight tilt of the patient backward and place the abdominal side of the patient nearer to the table edge. Although pneumoperitoneum created primarily through a veress needle, many surgeons prefer insertion of the primary trocar under direct vision to avoid the complications associated with the blind method, thought very small in number but more catastrophic than injuries associated with the open technique a pneumoperitoneum started up to a pressure of 15 mmHg. The second and third trocars inserted according to size and other anatomic factors of the spleen. In most cases, the fourth posterior trocar delayed until the splenic flexure of the colon has mobilized. Variation in trocar placement may include using a three instead of four trocars and experienced surgeons may replace one or two 12 mm trocars by 5 mm one.

Exploration and excision of accessory spleens: This needs medical reftraction of the stomach so that the spleen exposed. The accessory spleens should be looked for in all the known locations and once found, an accessory spleen must be removed immediately since once stained with blood, it will be difficult to relocate it. Accessory spleen excision is very important in ITP to prevent recurrence of the disease.

Mobilization of the lower pole: The splenocolic ligament incised to partially, mobilize the splenic flexure of the colon. An



2017Vol.3 No.3:21


extension of the incision slightly to the left side of the gastrocolic ligament gives a window to the gastrosplenic ligament. This latter now separated from the splenorenal ligament. This step will give a view of what called the splenic tent. The left and right walls of this tent consist of the gastrosplenic and splenorenal ligaments respectively and the floor consist of the stomach i.e. the lesser sac now opened laterally. By the use of electrocautery, the branches of the gastroepiploic artery can be controlled otherwise application of clips when these branches are large in size. The gsatrosplenic ligament now incised between the gastroepiploic artery and the short gastric arteries. This portion is avascular. A gentle retraction on the lower pole of the spleen at this stage will expose the hilar structures in the splenorenal ligament to assess the anatomy in this area to determine the level of difficulty and the need for a fourth trocar which can be inserted under vision posteriorly. Next, the phrenicocolic ligament should be incised up to the left crus of the diaphragm with the use of electrocautery leaving a small portion to help not only to suspend the organ but to help put it in the retrieval bag.

The splenic hilum: This depends much on the anatomy of the splenic vasculature. If they are of "distributed anatomy", they can be dissected and clipped. On the other hand, a "bundled anatomy" dealt with by a single use of a linear stapler after identification of the tail of the pancreas. A window opened in the splenorenal ligament above the hilar pedicle helps marking the ends of the stapler. The short gastric arteries taken in mass by the linear stapler or dissected and clipped.

Retrieval of the spleen: A medium or large size retrieval bag folded and introduced through one of the 12 mm trocars. When inside, it should be unfolded and the spleen slipped inside gently to avoid splenosis, facilitated by keeping the upper part of the phrenic splenic ligament intact which should be divided at this stage. Extraction done after a slight extension of the subcostal or umbilical incision. The bag edges held by a grasper inserted through the incision applying gentle traction will help in taking the spleen out to the surface. A suitable piece divided for biopsy, the spleen fragmented using the finger and the blood sucked out. Repeating this help in extraction of the bag and the remaining part of the spleen. At the end, a second look taken to make sure of hemostasis, the abdomen deflated, trocars removed and the incisions closed with absorbable sutures.

Follow up: All patients in the three groups were followed since admission till discharge, and at one week, one month, and 3 months after the procedure. In each visit, patients were evaluated clinically for evidence of bleeding and/or complications. Complete blood picture, liver function tests were done. We considered the response 2 weeks after the procedure as the initial response, and the response more than 2 months after the procedure as long-term response. Abdominal ultrasonography were performed to assess the existence of ascites, pleural effusion, portal vein thrombosis, postoperative collection or evidence of splenic abscess. Chest radiograph was obtained when indicated to exclude the possibility of pneumonia, atelectasis, or pleural effusion. For group II patients (PSE), U/S was done each visit to assess the extent of splenic infarction and to determine reduction

of splenic size after embolization. All tests or examinations could be repeated at any time depending on the clinical condition of the patient.

The obtained data were recorded in special performed sheet for statistical analysis. The data included patient demography, clinical presentation, information about past history of bleeding, hematemesis, results of laboratory investigations before and after treatment, findings in abdominal US and endoscopy, hospital stay, blood transfusion requirements, clinical course and morbidity and mortality (Figures 1-12).

Statistical analysisData collected throughout history, basic clinical examination, laboratory investigations and outcome measures coded, entered and analyzed using Microsoft Excel software. Data were then imported into Statistical Package for the Social Sciences (SPSS version 20.0) (Statistical Package for the Social Sciences) software for analysis.

According to the type of data, qualitative represents as number and percentage, quantitative continues group represent by mean ± SD, the following tests were used to test differences for significance.

Differences between frequencies (qualitative variables) and percentages in groups were compared by Chi-square test. Differences between parametric quantitative independent groups by t test paired by paired t.

P value was set at <0.05 for significant results and < 0.001 for high significant result.

ResultsOpen group (20 patients)65% of this group were male all of group were rural regard residence with mean age 48.8 ± 7.7 (Table 1).

There is improvement in Hb, WBC and platelet count postoperative and after one week follow up (Table 2).

The levels of Hb, WBC and platelet count return to normal level after one and three months of follow up (Table 3).

All cases with splenomegaly about two third with shrunken liver (Table 4).

Our study showed that one patient was died intraoperatively and one patient was with asymptomatic PV thrombosis postoperatively and 65% of patients had fever postoperatively (Table 5).

Our study shows that one patient had splenic bed collection after one month follow up and one patient with incisional hernia after three-month follow up (Table 6).

Our study shows one mortality (5%) (Table 7).

Significant changes in all items except between basic HB and Week HB also between HB and Month HB, also HB and three month HB finally POST HB and three month HB (Table 8).



2017Vol.3 No.3:21


Patient positioning for lateral approach.Figure 1

Ligation of splenic hilum with endoscopic stapler.Figure 4

Normal sized spleen in ITP patient after laparoscopic splenectomy.

Figure 5

Laparoscopic instruments.Figure 3

Laparoscopic port placement for lateral approach.Figure 2



2017Vol.3 No.3:21


Marking for midline incision for open splenectomy.Figure 6

Ligation of splenic artery and vein in open splenectomy.Figure 8

Midline incision for open splenectomy.Figure 7 Spleen after open splenectomy.Figure 9



2017Vol.3 No.3:21


Pre-embolization digital subtraction angiogram of splenic artery, arterial phase demonstrated normal appearance of splenic artery of the enlarged spleen 21 cm craniocaudal length.

Figure 10

Figure 12 Post-embolization digital subtraction angiogram of splenic artery after 70% embolization of the spleen had been achieved, demonstrating patent enhancement of the residual splenic parenchyma.

Pre-embolization digital subtraction angiogram of the splenic artery demonstrated normal blush of enlarged spleen.

Figure 11

Splenic artery embolization group (11 patients)63.3% of this group were male 72.7% of group were rural regard residence with mean age 50.36 ± 6.71 (Table 9).

Our study shows slight improveqment in Hb, WBC and platelet count postoperatively and one week of follow up (Table 10).

There is more improvement in Hb, WBC and platelet count after one and three months of follow up (Table 11).

54.5% of the patients were with ascites and all patients were presented with splenomegaly (Table 12).

All patients were presented with post-embolization syndrome postoperatively and 27.3% of the patients were presented with ascites (Table 13).

One patient was presented with splenic abscess after one-month follow up and there was reduction in splenic size in 45.5% of the patients after three months of follow up and we had one uraemic patient and two patients with HCC (Table 14).

Our study shows no mortality (Table 15).

Significant changes base PLT and week, month and three month also between post and three month PLT (Table 16).



2017Vol.3 No.3:21


Open group (20 patients) Mean ± SD (range)Age 48.8 ± 7.7 (33-70)

N %

SexMale 13 65.0

Female 7 35.0Residence Rural 20 100.0

Table 1 Socio-demographic distribution.

POSTHB POSTWBC POSTPLT Week HB Week WBC Week PLTMean 12.91 ± 1.5 11.98 ± 6.3 125.0 ± 41.7 12.02 ± 1.04 10.0 ± 2.7 239.36 ± 164.2

Minimum 10.50 6.10 76.00 9.90 6.20 90.00Maximum 15.10 31.50 217.00 13.60 17.50 842.00

Table 2 Distribution of blood picture of post operation and one week of follow up after exclusion of one died case (n=19).

Month HB Month PLT Month WBC Three month HB Three month WBC Three month PLTMean 12.06 ± 1.19 277.0 ± 104 8.89 ± 1.6 12.06 ± 1.3 8.9 ± 1.7 259.57 ± 68.6

Minimum 10.20 130.00 5.30 8.80 6.00 177.00Maximum 14.50 510.00 12.60 14.30 12.50 500.00

Table 3 Distribution of blood picture of one and three month of follow up after exclusion of one died case (n=19).

N %

Shrunken liverNo 7 35.0Yes 13 65.0

Enlarged liverNo 14 70.0Yes 6 30.0

Splenomegaly Yes 20 100.0Ascites No 20 100.0

Total 20 100.0

Table 4 Sign distribution.

N %

Liver functionDied 1 5.0

Elevated 10 50.0No 9 45.0

BleedingDied 1 5.0No 19 95.0

FeverDied 1 5.0No 6 30.0Yes 13 65.0

HematemesisDied 1 5.0No 19 95.0

MelenaDied 1 5.0No 19 95.0

AscitesDied 1 5.0No 19 95.0

Hepatic dysfunctionDied 1 5.0No 9 45.0Yes 10 50.0

Other

Died 1 5.0Chest infection 6 30.0Hematemesis 1 5.0

No 11 55.0P.V thrombosis 1 5.0

Total 20 100.0

Table 5 Distribution of post operation characters.



2017Vol.3 No.3:21


N %

One week


Elevated 2 10.0N 17 85.0

Kidney functionDied 1 5.0

N 19 95.0

WoundDied 1 5.0clean 15 75.0

Infected 4 20.0

One month


Elevated 4 20.0N 15 75.0


N 19 95.0

US

Died 1 5.0Free 16 80.0

P.V thrombosis 1 5.0Splenic bed collection 1 5.0

U.B diverticulum 1 5.0

Three month


Elevated 1 5.0No 18 90.0


N 19 95.0

US

Died 1 5.0Free 16 80.0

Ascites 1 5.0Incision hernia 1 5.0

Recanalization PV thrombosis 1 5.0Total 20 100.0

Table 6 Follow up after one week one month and three month.

N %

MortalitySurvived 19 95.0

Died 1 5.0Total 20 100.0

Table 7 Mortality distribution.

Laparoscopic group (4 patients)100% of this group were female half of group were rural regard residence with mean age 35.25 ± 12.3 (Table 17).

Our study shows improvement in Hb, WBC and platelet count postoperatively and after one-week follow up (Table 18).

There is more improvement in Hb, WBC and platelet count after one and three months of follow up (Table 19).

All patients were with normal-sized spleen (ITP) (Table 20).

75% of the laparoscopic splenectomy were converted to open method (Table 21).

Our study shows that one patient had gastric fistula postoperatively (Table 22).

Our study shows one mortality (25%) (Table 23).

Significant changes between basic PLT and one week and three month PLT (Table 24).

Embolization is a simple and rapid procedure espcialy for child B patients (Table 25).

Emblization associated significantly with elevated liver function and we had one mortality with open spelenctomy and no mortality with embolization (Table 26).

DiscussionHypersplenism is a clinical syndrome characterized by: splenomegaly, although this may be only moderate, pancytopenia or a reduction in the number of one or more types of blood cells, neutropenia is less common than anemia and thrombocytopenia, normal production or hyperplasia of the precursor cells in the marrow or a so called maturation arrest, decreased red blood cells survival and decreased platelet survival. In hypersplenism, its normal function accelerates, and begins automatically to remove cells that may still be normal in function. Sometimes, the spleen wills temporarily sequester 90% of the body platelets and 45% of the red cells [10].



2017Vol.3 No.3:21


Mean SD Paired t PHB 11.4053 1.98312

-2.760 0.013POSTHB 12.9105 1.52202

HB 11.4053 1.98312-1.261 0.224

Week HB 12.0263 1.04341HB 11.4053 1.98312

-1.133 0.272Month HB 12.0684 1.19724

HB 11.4053 1.98312-1.126 0.275

Three month HB 12.0684 1.34125POSTHB 12.9105 1.52202

1.955 0.066Three month HB 12.0684 1.34125

WBC 3.6474 2.23094-5.768 0.00

POSTWBC 11.9895 6.36482WBC 3.6474 2.23094

-6.934 0.00Week WBC 10.0053 2.77738

WBC 3.6474 2.23094-8.077 0.00

Month WBC 8.8947 1.60433WBC 3.6474 2.23094

-7.559- 0.00Three month WBC 8.9042 1.75268

POSTWBC 11.9895 6.364821.997 0.061

Three month WBC 8.9042 1.75268PLT 47.3684 18.23675

-8.041 0.00POSTPLT 125.0000 41.72396

PLT 47.3684 18.23675-4.345 0.00

Week PLT 239.3684 189.57268PLT 47.3684 18.23675

-9.246 0.00Month PLT 277.0000 104.06515

PLT 47.3684 18.23675-12.213 0.00

Three month PLT 259.5789 68.60865POSTPLT 125.0000 41.72396

-8.422 0.00Three month PLT 259.5789 68.60865

Table 8 Blood picture comparison between different times.

Splenic artery embolization group (11 patients) Mean ± SD (range)Age 50.36 ± 6.71 (36-58)

N %

SexMale 7 63.3

Female 4 36.4

ResidenceRural 8 72.7Urban 3 27.3


POSTHB POSTWBC POSTPLT Week HB Week WBC Week PLTMean ± SD 12.08 ± 2.01 5.15 ± 3.04 58.63 ± 19.8 11.44 ± 1.7 4.34 ± 1.8 104.0 ± 66.02Minimum 9.10 1.45 18.00 9.20 2.70 72.00Maximum 15.60 12.00 80.00 15.20 7.50 301.00

Table 10 Distribution of blood picture of post operation and one week of follow up.

Month HB Month PLT Month WBC Three month HB Three month WBC Three month PLTMean 11.71 ± 1.7 100.54 ± 69.7 4.28 ± 2.5 10.99 ± 1.2 4.02 ± 1.2 101.45 ± 62.4

Minimum 9.80 40.00 1.70 9.00 2.40 45.00Maximum 15.60 300.00 11.20 13.80 6.00 280.00

Table 11 Distribution of blood picture of one and three month of follow up.



2017Vol.3 No.3:21


N %

One weekLiver function

Elevated 5 45.5N 6 54.5

Kidney function N 11 100.0Wound Clean 11 100.0

One month

Liver functionElevated 6 54.5

N 5 45.5

Kidney functionE 1 9.1N 10 90.9

US

Free 5 45.5Ascites 2 9.1

splenic abscess 1 9.1HCC 2 18.2

Uremic 1 9.1

Three month


N 5 45.5Kidney function N 11 100.0

Reduction in spleen sizeYes 5 45.5No 6 55.5

US

Free 5 45.5Ascites 2 18.2

Ascites and splenic abscess 1 9.1HCC 2 18.2

Uremic 1 9.1Total 11 100.0



N %Shrunken liver Yes 11 100.0Splenomegaly Yes 11 100.0

AscitesNo 5 45.5Yes 6 54.5

Total 11 100.0

N %


N 3 27.3Bleeding No 11 100.0

Fever Yes 11 100.0Hematemesis No 11 100.0

Melena No 11 100.0

AscitesNo 8 72.7Yes 3 27.3

Hepatic dysfunctionNo 3 27.3Yes 8 72.7

OtherPost embolism syndrome 11 100.0

Total 11 100.0

Table 13 Distribution of post operation characters.

Frequency PercentMortality Survived 11 100.0

Table 15 Mortality.



2017Vol.3 No.3:21


Mean Std. Deviation Paired t PHB 11.5727 2.09575

-1.493 0.166POSTHB 12.0818 2.01038

HB 11.5727 2.095750.233 0.821

Week HB 11.4455 1.71893HB 11.5727 2.09575

-0.247 0.810Month HB 11.7182 1.73425

HB 11.5727 2.095750.772 0.458

Three month HB 10.9909 1.28954POSTHB 12.0818 2.01038

1.484 0.169Three month HB 10.9909 1.28954

WBC 3.9145 1.64022-1.411 0.189

POSTWBC 5.1555 3.04730WBC 3.9145 1.64022

-1.106 0.295Week WBC 4.3455 1.87102

WBC 3.9145 1.64022-0.442 0.668

Month WBC 4.2818 2.56040WBC 3.9145 1.64022

-0.206 0.841Three month WBC 4.0273 1.26577

POSTWBC 5.1555 3.047301.204 0.256

Three month WBC 4.0273 1.26577PLT 54.0909 16.10872

-1.056 0.316POSTPLT 58.6364 19.82056

PLT 54.0909 16.10872-2.686 0.023

Week PLT 104.0000 66.02575PLT 54.0909 16.10872

-2.432 0.035Month PLT 100.5455 69.79737

PLT 54.0909 16.10872-2.799 0.019


-2.461 0.034Three month PLT 101.4545 62.42333


Laparoscopic group (4 patients) Mean ± SD (range)Age 35.25 ± 12.3 (23-52)

N %

SexMale 0 0.0

Female 4 100.0

ResidenceRural 2 50.0Urban 2 50.0



Minimum 11.10 90.00 7.80 11.10 8.80 195.00Maximum 13.90 365.00 12.20 12.30 10.50 268.00

Table 18 Distribution of blood picture of post operation and one week of follow up.


Minimum 11.10 90.00 7.80 11.10 8.80 195.00Maximum 13.90 365.00 12.20 12.30 10.50 268.00

Table 19 Distribution of blood picture of one and three month of follow up after exclusion of one died case (n=3).



2017Vol.3 No.3:21


N %Shrunken liver No 4 100.0Enlarged liver No 4 100.0Splenomegaly No 4 100.0

Ascites No 4 100.0


Frequency PercentLiver function Normal 4 100.0

Bleeding No 4 100.0Fever Yes 4 100.0

Hematemesis No 4 100.0Melena No 4 100.0

Hepatic dysfunction No 4 100.0

Other, lap. Converted to open methodYes 3 75.0No 1 25.0

Table 21 Distribution of postoperative characters.

N %

One week


No 3 75.0Kidney function N 4 100.0

WoundClean 2 50.0

Gastric fistula 1 25.0Infected 1 25.0

One month


N 3 75.0


N 3 75.0

USDied 1 25.0Free 3 75.0

Three month


N 3 75.0


N 3 75.0

USDied 1 25.0Free 3 75.0Total 4 100.0


Frequency Percent

MortalitySurvived 3 75.0

Died 1 25.0Total 4 100.0

Table 23 Mortality.

Hypersplenism is a triad of splenomegaly, pancytopenia and normocellular bone marrow [11]. Blood transfusions may be required. Open or laparoscopic splenectomy may be indicated to control or stage the disease (eg hereditary spherocytosis, Hodgkin's disease). Patients with impaired splenic function need prophylactic vaccinations etc. [1].

In our study open splenctomy was done in 20 patients, midline in cision was done in all patients under general anesthesia. The mean time of splenctomy with devascularization was two hour. Blood transfusion was needed in all patients.

The rise in the platelet count results from increased production from bone marrow that splenic artery ligation has the same effect on the formed elements of the blood but due to development, this effect is temporary.

In our study improvement in platelet, WBCs and hemoglobin occurred in all patients who underwent splenctomy and this maintained during follow up period. These results are similar to that of Sundaresan et al. [3] who found improvement in all three cell lines occurred in all the 16 patients (100%) and this maintained in all of those who were followed up for three months, however,



2017Vol.3 No.3:21


Mean Std. Deviation Paired t PHB 11.2250 1.56498

-0.090 0.934POSTHB 11.3250 .78049

HB 11.2250 1.56498-0.033 0.976

Week HB 11.2500 .95394HB 12.0000 .26458

-0.122 0.914Month HB 12.1000 1.56205

HB 12.0000 .264580.504 0.664

Three month HB 11.7667 .61101POSTHB 11.0000 .52915

-1.206 0.351Three month HB 11.7667 .61101

WBC 10.8750 4.92231-2.123 0.124

POSTWBC 17.2750 6.40332WBC 10.8750 4.92231

-0.199 0.855Week WBC 11.7250 4.25627

WBC 12.4000 4.731810.853 0.483

Month WBC 10.4667 2.34379WBC 12.4000 4.73181

1.032 0.410Three month WBC 9.3667 .98150

POSTWBC 18.5333 7.211332.476 0.132

Three month WBC 9.3667 .98150PLT 104.0000 90.24781

-1.258 0.297POSTPLT 146.2500 28.92951

PLT 104.0000 90.24781-4.223 0.024

Week PLT 196.0000 80.02916PLT 63.0000 46.16276

-2.015 0.182Month PLT 219.3333 138.22566

PLT 63.0000 46.16276-4.925 0.039


-3.063- 0.092Three month PLT 225.6667 37.87259


the results of the previous studies on the effect of splenctomy, though good, have not been so overwhelming.

In our study, as regard hemoglobin concentration, there was no significant increase in its value 2 weeks and 3 months post splenectomy.

In our study we had one mortality (5%) due to uncontrollable intraoperative bleeding during dissection on aneurysm in the splenic artery near coeliac trunk.

Amin et al. [12] had no mortality among his patients for follow up period of at least 6 months.

In our study there was one patient with portal vein thrombosis (5%) was detected by systemic imaging duplex the patient was asymptomatic and eventuality resolved by anticoagulant.

Amin et al. [12] had three patients developed postoperative portal vein thrombosis that was complete in one case who presented latter with mesenteric vascular occlusion] and partial in the other two cases.

In our study there was one patient developed ascites (5%) after 3 months follow up and this due to patient was child class A preoperative and after 3 months patient was child class B with low albumin level and was treated by liver support and diuretic

therapy. Amin et al. [12] had two patient (10%) developed ascites that was controlled successfully by salt restriction and diuretic therapy.

In our study there was one patient (5%) with splenic bed collection. Patient presented with left hypochondrial pain and fever more than 39c and increased WCBs count, patient investigated by ultrasound who shows splenic bed collection which managed by APOCATH insertion after that fever and WBCs count decrease and patient improved. Amin et al. [12] had no patients reported with splenic bed collection.

In our study we had one patient (5%) with incisional hernia after three months follow up and managed by hernioplasty. Amin et al. [12] had no patients reported with incisional hernia.

In our study we had 13 patients (65%) with fever postoperative, some of them due to chest infection managed by triple antibiotics and chest physiotherapy, the others due to wound infection, managed by repeated dressing.

OPSI did not occur in any of our splenctomied patient during follow up period. This can be explained by the use of pneumococcal vaccine before splenctomy and also the age of our patients is above 30 years but the risk of OPSI is still present in our study.



2017Vol.3 No.3:21


GROUPTotal X2 P

Open Embolization

End Liver function

DiedCount 1 0 1

10.16 0.006

% 5.0% 0.0% 3.2%

ElevatedCount 1 6 7

% 5.0% 54.5% 22.6%

NormalCount 18 5 23

% 90.0% 45.5% 74.2%

End kidney functionDied

Count 1 0 1

0.56 0.45% 5.0% 0.0% 3.2%

NormalCount 19 11 30

% 95.0% 100.0% 96.8%

MortalitySurvived

Count 19 11 30

0.56 0.45% 95.0% 100.0% 96.8%

DiedCount 1 0 1

% 5.0% 0.0% 3.2%

TotalCount 20 11 31

% 100.0% 100.0% 100.0%

Table 26 Comparison at end of follow up and mortality.

GROUPTotal X2 P

Open Mobilization

Postliver function

DiedCount 1 0 1

1.75 0.41

% 5.0% 0.0% 3.2%

ElevatedCount 10 8 18

% 50.0% 72.7% 58.1%

NCount 9 3 12

% 45.0% 27.3% 38.7%

BleedingDied

Count 1 0 1

0.56 0.45% 5.0% 0.0% 3.2%

noCount 19 11 30

% 95.0% 100.0% 96.8%

Fever

DiedCount 1 0 1

4.97 0.08

% 5.0% 0.0% 3.2%

NoCount 6 0 6

% 30.0% 0.0% 19.4%

YesCount 13 11 24

% 65.0% 100.0% 77.4%

Post HeamatemisisDied

Count 1 0 1

0.56 0.45% 5.0% 0.0% 3.2%

NoCount 19 11 30

% 95.0% 100.0% 96.8%

Post MelenaDied

Count 1 0 1

0.56 0.45% 5.0% 0.0% 3.2%

NoCount 19 11 30

% 95.0% 100.0% 96.8%

Post Ascites

DiedCount 1 0 1

8.65 0.03

% 5.0% 0.0% 3.2%

NoCount 19 8 26

% 95.0% 72.7% 83.9%

YesCount 0 3 3

% 0.0% 27.3% 9.7%

TotalCount 20 11 31

% 100.0% 100.0% 100.0%

Table 25 Comparison after operation between two groups.



2017Vol.3 No.3:21


Selective splenic angiography was done in 11 patients. The right femoral route was used in all patients. The procedures were done under local anesthesia. The value of splenic angiography in detecting focal lesions of the spleen as cysts and aneurysms has been described by Sindel et al. [13]. In our study no focal lesion was detected by the splenic angiography.

Different embolic agents can be used for PSE including coils, gel foam and other embolic agents. Recnt studies concluded that particles especially PVA is safe and effective for PSE. Kontchou et al. [14] have used polyvinyl alcohol foam or microspheres ranged from 200 to 1000 Mm depending on the diameter of the catheter in 31 patients. They used cyanoacrylate with a dilution ratio in lipidol 1/1 in one patient.

In our study we used gel foam as it is cheap and available and we had one patient had recurrence after embolization.

Partial splenic embolization under antibiotic protection has been suggested in recent reports to avoid the high rate of complications associated with total splenic embolization with the assumption that the intact splenic parenchyma remaining after partial embolization provides enough protection from bacterial infection. While total occlusion of splenic artery may lead to reversal of flow in the splenic veins, carrying bacteria that may be circulating in the portal system into the infracted spleen causing splenic abscess despite antibiotic protection [8].

The response to splenic artery embolization was evaluated by clinical examination, laboratory studies, abdominal u/s, all patients underwent follow up studies at 1 week, 1 month and three months.

The most important topic to stress upon during clinical evaluation is post embolization syndrome, PES, described by Tajiri et al. [15].

In our study, pain occurred in all our patients. It started immediately after embolization in the region of the spleen it was mild and moderate in all patients and relieved by non-steroidal anti-inflammatory. Amin et al. [12] shows pain was severe only in 2 patients from 20 patient who needed morphine administration.

Fever always accompanied pain in our study fever was mild in most of our patients, not exceeded 30c. PSE was significantly rapid procedure, the mean time taken in PSE from sterilization till post embolization angiogram was about 30 minutes.

No blood transfusion was needed was needed pre or post embolization, also PSE patients had significaly short period of hospital stay as they discharged from the the hospital [the mean about 2 days] after improvement of post embolization syndrome.

In our study, improvement in platelet, WBCs and hemoglobin occurred in all patients but platelet count decrease during follow up period but not as pre embolization level. PSE increases platelet count via two mechanisms; by reducing the trapping of thrombocytes in the embolized spleen and by decreasing level of platelet associated IgG. Reduction of platelet associated IgG leads to decreased immunologic induction of thrombocytopenia. The increase WBCs was due to activation of body defense mechanism against dead splenic tissues [16].

The efficacy of PSE observed in our study confirm the results of previously published studies in patients with hypersplenism, marked improvement in platelet count occurred in all patients and remained high for several months, Yoshida et al. [8] found that serum albumin level increased after PSE. They also concluded that PSE can be benefits patients with cirrhosis by improving the capacity for hepatic protein synthesis.

In our study slight decrease in spleen size about 2 to 3 cm in 5 patients after 3 months follow up, Watanabe et al. (1996) observed that spleen enlarged to 110%to 130% of pre PSE volume 1 to 2 weeks after embolization probably due to necrosis and oedema of surrounding parenchyma then splenic size decreased gradually owing to resorption of necrotic tissue. Amin et al. [12] shows a significant decrease in splenic volume after PSE.

In our study, no mortality occurred in our patients during follow up period. Amin et al. [12] had one mortality in 20 patients due to myocardial infarction precipitated by severe pain that follows PSE.

In our study, no portal vein thrombosis was detected in our patients. Amin et al. [12] had one patient with portal vein thrombosis but was asymptomatic and managed by anti-coagulant, they argued that splenic embolization may enhance venous thrombosis in same manner as splenctomy due to alteration in the blood composition and stasis of blood in the splenic veins.

In our study 2 patients (18.2%) had ascites after three months follow up as the two patients was child B with ascites pre embolization. Kontchou et al. [14] observed transient ascites in two of his patients with child class A and B before the procedure but ascites resolved with medical treatment in 15 and 45 days.

In our study splenic abscess occurred in one patient. The clinical manifestation was markedly delayed occurring about one month after hospital discharge. A Large cystic necrosis of the spleen was observed at one month on ultrasound. Patient had severe abdominal pain and fever more than 39c. Patient was treated with splenctomy. Amin et al. [12] had one patient with splenic abscess treated with splenctomy.

In our study pancreatitis did not occur in any of our patients this mainly due to we delivered gel foam distal to origin of pancreatic branches. Kumpe et al. [17] recorded one patient with mild increase in amylase, although he did not have clinical pancreatitis.

Laparoscopic splenctomy can be considered as a safe and effective procedure in benign hematological diseases especially ITP. It provides the advantage of minimally invasive surgery with low morbidity and mortality compared with open splenctomy.

Cueto-Ramos et al. [18] did 14 laparoscopic splenctomy from 2008 to 2014, one patient converted to open method and had no mortality, and the main complain of the patients was purpura and during follow-up platelet count improved within two weeks post-operative.

In our study number of our patients was too small 4 patients,all



2017Vol.3 No.3:21


patients was female and the main complaint was purpura, we had one motality (25%) during follow up due to gastric fistula. Also three patients converted to open methods (75%) due to uncontrollable intraoperative bleeding and aslo due to lack of experience of the surgeon.

Also in our study one patient do lap splenctomy till the end, and the drain removed in the 2nd day and discharged in the 4th day postoperatively.

In our study, improvement in platelet, WBCS count and hemoglobin occurred in all patients who underwent laparoscopic splenctomy and this maintained during the follow up period.

LimitationsOur study has limitations; the number of patients was small; also, patients were belonging only to Child A or B and not belonging to Child C severity grading system.

Conclusion• Our study shows that open splenectomy is a good

operation for patients with hypersplenism especially Child A group, with little postoperative complications.

• Our study suggests that Partial Splenic Embolization (PSE) is a good alternative to splenectomy in patients with hypesplenism, especially Child B group; it improves cytopenias, shrinks the splenic size, and preserves the splenic vein for further surgery if required. PSE has the advantage of non-operative intervention and being performed under local anesthesia; in addition, it allows preservation of adequate splenic tissue and thereby prevents the overwhelming infection.

• Laparoscopic splenectomy is a good operation for ITP patients, but still needs more training, more experience and more cases to improve the results.

References1 Pozo AL, Godfrey EM, Bowles KM (2009) Splenomegaly: investigation,

diagnosis and management. Blood Rev 23: 105-11.

2 Liu M, Hsieh C, Chang T, Lin JP, Huang CC (2004) Radiotherapy for hyperpslenism from congestive splenomegaly. Ann Saudi Med, pp: 198-200.

3 Sundaresan JB, Dutta TK, Badrinath S, Jagdish S, Basu D (2005) Study of hypersplenism and effect of splenectomy on patients with hypersplenism. JIACM 6: 291-6.

4 Henry PH, Longo DL (2001) Enlargement of the lymph nodes and spleen. In: Braunwald E, Fauci AS, Kasper DL (eds.) Harrison’s Principle of Internal Medicine, (15thedn), New York: McGraw-Hill, pp: 360-365.

5 Zhu JH, Wang YD, Ye ZY, Zhao T, Zhu YW, et al. (2009) Laparoscopic versus open splenectomy for hypersplenism secondary to liver cirrhosis. Surg Laparosc Endos c Percutan Tech 19: 258-62.

6 Maddison FE (1973) Embolic therapy of hypersplenism. In rest Radiology 8: 280-300.

7 Vujic I, Lauver JW (2001) Severe complications from partial splenic embolization in patients with liver failure. Br J Radiol, pp: 492-5.

8 Yoshida H, Mamada Y, Taniai N, Yamamoto K, Kaneko M, et al. (2005) Long-term results of partial splenic artery embolization as supplemental treatment for portal-systemic encephalopathy. Am J Gastroenterology 100: 43.

9 Abdallah HM, Abdel Moez AT, Abu El-Maaty ME, Helmy AZ (2010) Role of partial splenic arterial embolization for hypersplenism in patients with liver cirrhosis and thrombocytopenia. Ind J Gastroenter 29: 59-61.

10 Edwards, CRW, Bouchier IAD (2009) Splenomegaly. Davidson's

Principles and Practice of Medicine, (17thedn), Toronto: Churchill Livingstone, pp: 305.

11 Elmakki E (2012) Hypersplenism: Review article. J Bio, Agri Healthcare 2: 89-99.

12 Amin MA, El Gendy MM, Dawoud IE, Shoma A, Negm AM, et al. (2009) Partial splenic embolization versus splenectomy for the management of hypersplenism in cirrhotic patients. World J Surg 33: 1702-1710.

13 Sindel M, Sarikcioglu L, Ceken K, Yilmaz S (2001) The importance of the anatomy of the splenic artery and its branches in splenic artery embolization. Folia Morphol 60: 333-336.

14 Kontchou G, Seror O, Bourcier V, Mohand D, Ajavon Y, et al. (2005) Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long term outcome in 32 patients. Eur J Gastroenterol Hepatol 17: 179.

15 Tajiri T, Onda M, Yoshida H, Mamada Y, Taniai N, et al. (2002) Long term hematological and biochemical effects of partial splenic embolization in hepatic cirrhosis. Hepatogastroenterology 49: 1445.

16 Firat A, Boyvat F, Moray G, Aytekin C, Karakayali H, et al. (2005) Comparison of two different percutaneous splenic artery interventions in the treatment of hypersplenism: preliminary report. Transplant Proc 37: 1094.

17 Kumpe DA, Rumack CM, Pretorious DH, Stoecker, TJ, Stellin GP (1985) Partial splenic embolization in children with hypersplenism. Radiology 155: 357.

18 Cueto-Ramos RG, Munoz-Maldonado GE, Hernandez-Guedea MA, Fernández-Treviño JR, Limas-Rodríguez QG (2015) Laparoscopic splenectomy experience in the university hospital. Medicina Universitaria 17: 38-41.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=19062140

Documents

Evaluation of Three Methods of Treatment of Hypersplenism...Hypersplenism is characterized by cytopenia, splenomegaly, increased or normal medullar cellularity, and elevated turnover