Blood Coagulatio

n

Haemostasispart3

DICLab: - fibrinogen

- platelet- PT- aPTT- fibrin degradation product

acute DIC: - prolongation of aPTT, PT and TT- reduction of platelets, AT III and protein C- decreased fibrinogen- elevated fibrin degradation products

chronic DIC: - aPTT and PT may be within normal ranges- slightly decreased platelets- elevated fibrin degradation products and

D-dimer

Platelet Functional Abnormalities congenital

1. Bernard-Soulier syndrome• defect in platelet adhesion• autosomal recessive• defect in platelet membrane glycoprotein (GP Ib)

2. thrombasthenia• defect in platelet aggregation• autosomal recessive• defect in platelet membrane glycoprotein (GP IIb & IIIa)• no fibrinogen linking of platelets• easy bleeding and no clot retraction

1

2

Platelet Functional Abnormalities acquired

1. aspirin• inhibits cyclooxygenase

suppression of TXA2 synthesis• effect lasts for 72 hours

2. thrombocythemia• platelet : >3,000,000/ml• functionally abnormal platelets• occasionally seen in myeloproliferative disorders

Approach to the diagnosis of bleeding disorder

Clinical Evaluation History

Physical ExaminationFamily history

Laboratory EvaluationScreening testSpecific test

Clinical Features of Bleeding Disorders Platelet disorders Coagulation

disorders

Site of bleeding Skin Deep in soft tissues (epistaxis, gum, Mucous vaginal, GI tract) membranes,

joints, muscles) Petechiae Yes No

Ecchymoses (“bruises”) Small, superficial Large, deep

Hemarthrosis / muscle bleeding Extremely rare Common

Bleeding after cuts & scratches Yes No

Bleeding after surgery or trauma Immediate, Delayed (1-2

days), usually mild often severe

Platelet Coagulation

Petechiae, Purpura Hematoma, Joint bl.

Tests for Primary Hemostasis• Bleeding time platelet & vascular phases• PFA – 100 system Platelet function

• Platelet count Quantification of platelets

• Blood smear Quantitative & morphological abnormalities of platelets , Detection of underlying haemotological disorder

PLATELET COUNT

NORMAL 150,000 - 400,000 CELLS/MM3

< 100,000 Thrombocytopenia

50,000 - 100,000 Mild Thrombocytopenia

< 50,000 Sev Thrombocytopenia

BLEEDING TIME

PROVIDES ASSESSMENT OF PLATELET COUNT AND FUNCTION

NORMAL VALUE 2-8 MINUTES

Laboratory diagnosis of the coagulopathies

Contact activation Tissue thromboplastin (TF)

XII

XI

IX

VIII

VII

X

V

II

I

INTRINSIC EXTRINSIC

COMMON

Blood coagulation time

APTI

Prothrom-bin

Fibrin

INR

INR: International normalized ratio

-was established by the WHO and the International Committee on Thrombosis and Hemostasis for reporting the results of prothrombin tests

-All PT results are standardized by this calculation:

INR= ( Patient PT / Control PT)ISI

ISI= International sensitivity index

- Given by the manufacturer for each particular thromboplastin reagent and instrument combination

ACTIVATED THROMBOPLASTIN TIME

Measures Effectiveness of the Intrinsic Pathway & common pathway

NORMAL VALUE 25-40 SECS

APTT prolongs..

1. Intrinsic pathway factor deficiencies (FXII, XI,VIII, IX, HMWK, prekallikrein )

- Inherited or acquired- Consumption (DIC)- PIVKA factors in cumarin therapy

2. Specific inhibitors against FXII, XI, VIII, IX, HMWK, prekallikrein

3. Lupus anticoagulant

4. Non-fractionated heparin therapy

THROMBIN TIME Time for Thrombin To Convert

Fibrinogen Fibrin A Measure of Fibrinolytic Pathway

NORMAL VALUE 9-13 SECS

TT Prolongs..

1. Hypo- afibrinogenaemia2. Dysfibrinogenaemia3. Non fractionated heparin 4. Fibrinogen/ fibrin degradation product s5. Chronic liver disease

Platelet count

Bleeding time

APTI Prothrom-bin

Presumptive diagnosis

Decreased Prolonged Norm. Norm. Thrombocytopenia

Norm. Prolonged Prolonged Norm. von Willebrand’s disease

Norm./ increased

Prolonged Norm. Norm. Thrombocytopathia

Norm. Norm. Prolonged Norm. „intrinsic” pathway abnormality (FVIII. IX. XI. XII)

Norm. Norm. Norm. Prolonged „extrinsic”pathway abnormality (FVII)

Norm. Norm. Prolonged Prolonged „common” pathway abnorm. (FI. II. V. X.)

Norm. Norm. Norm. Norm. - /FXIII deficiency/ milde bleeding disorder

Diagnosis of bleeding disorders by the screening tests

ANTICOAGULATION & FIBRINOLYSIS

Vascular WallAnti-Coagulation Factors

Fibrinolytic Factors

ANTICOAGULATION & FIBRINOLYSISVascular Wall

• Endothelial Cell• prostacyclin (PGl2)• heparan sulfate• thrombomodulin• tissue plasminogen activator (tPA)

• Muscle• muscular dilation

Protein C• vit K dependent zymogen• produced in liver• inactivates Va and VIIIa

Protein S• vit K dependent binding protein• co-factor for protein C• binds C4b-binding protein

II

XII

XI

IX

VIII VII

X

V

I

XIII

Stable clot

AnticoagulationHeparin

• Heparin activates Antithrombin III (AT III)• AT III inactivates Thrombin and Factor Xa• rapid onset of action

Laboratory monitoring:• aPTT : ~1.5X – 2.5X normal mean• heparin level :

0.2 – 0.4 U/mL by protamine titration

0.35 – 0.70 by Factor Xa inactivation assay

II

XII

XI

IX

VIII VII

X

V

I

XIII

Stable clot

AnticoagulationHeparin

AT AT

II

II

AT

II

AT

II

AT

II

AT

II

AT

Coumadin (Warfarin) Anticoagulants

•inhibits hepatic synthesis of vit K-dependent clotting factors (II, VII, IX, X)•competitive inhibition of g-carboxylation

inactivate “acarboxy” forms synthesized

•onset delayed 3 to 5 days•also inhibits synthesis of protein C & S

II

XII

XI

IX

VIII VII

X

V

I

XIII

Stable clot

Coagulation Tests1. Bleeding Time : in vivo test

measures adequacy of plt functionnormal : <6 min.

2. Platelet Count normal : >200,000/mL3. aPTT : intrinsic pathway (XII, XI, IX, VIII, X, V)

used to guide heparin therapy4. 50/50 mixing study

pt’s plasma + nl. plasmaif mixing correct aPTT = Pt is deficient in intrinsic factor(s)no correction = circulating anticoagulants or inhibitors

5. Prothrombin Time (PT) : extrinsic pathway (II, VII, V, X)monitoring warfarin/coumadin effects

Coagulation Tests

6. Fibrinogen Level normal : 200 – 500 mg/dL7. ADP platelet aggregation8. Ristocetin aggregation test

• test for presence or activity of vWF9. Thrombin Time (TT) normal : 20 – 30 sec

• measures 3rd stage of coagulation• prolonged if

• def or abnormality of fibrinogen• presence of fibrin split products• presence of heparin

History & Physical Examare

most importantmost sensitivemost specific

Tests of Hemostasis

Antithrombin III (AT III)

• naturally-occuring anticoagulant

• binds to factors IXa, Xa, XIa, XIIa (slow)

• accelerated by heparin manyfold

Implication:

Heparin has almost NO anticoagulant

action without AT III

Coagulation Factors

FACTORS PLASMA t ½ (hrs)

Fibrinogen (I) 72-120

Prothrombin (II)

60-70

V 12-16

VII 3-6

VIII 8-12

IX 18-24

X 30-40

FACTORS PLASMA t ½ (hrs)

XI 52

XII 60

Protein C 6

Protein S (total)

42

Tissue factor --

Thrombomodulin

--

antithrombin 72

Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30.

Fibrinolysis

• Plasminogen → plasmin

• Release of tPA by the endothelium

• Lysis of clot→ FDPs or FSPs

• Reopening of blood vessel

Laboratory MonitoringProthrombin Time (PT)

• test of extrinsic pathway activity

• measures vitamin K - dependent factors activity

(factors II, VII, IX, X)

• thromboplastin + Ca+2 to plasma = clotting time

• normal values: 12-14 seconds

• International Normalized Ratio (INR)▪ standardizes PT reporting

• normal values: 0.8 -1.2 seconds

Laboratory Monitoring Prothrombin Time (PT)

• monitors coumadin therapy

• most sensitive to alteration in F VII levels

• prolonged: 55 % ↓ of normal F VII activity

• antithrombotic activity: reduction of factor II

and factor X activity (after several days)

Laboratory Monitoring Activated Partial Prothrombin Time (aPTT)

• test for intrinsic and common pathways

• dependent on activity of all coagulation factors, except

VII and XIII

• normal values: 25 -35 seconds

• monitors heparin tx & screen for hemophilia

Laboratory Monitoring Activated Prothrombin Time (aPTT)

• prolonged: heparin, thrombin inhibitors,

fibrin degradation products (FDP)

• citrated plasma + surface activators +

phospholipid

• prolonged only if coagulation factors reduced to <

30 % of normal

Laboratory Monitoring Activated Clotting Time (ACT)

• monitors heparin anticoagulation in the OR

(cardiac and vascular surgeries)

• normal values: 90 - 120 seconds

Laboratory MonitoringThrombin Clotting Time (TCT)

• reflects abnormalities in fibrinogen → fibrin

• plasma + excessive amount of thrombin

• prolonged: heparin, thrombin inhibitors,

low fibrinogen, dysfibrinogenemia

• monitors hirudin, bivalirudin, LMWH tx

• INR & PT may be normal or ↑

• TCT prolonged with adequate therapeutic levels

Laboratory Monitoring

Thromboelastography (TEG)

• continuous profiles during all phases of

clot formation

• provides more accurate picture of in vivo

coagulation process• to evaluate:

• hypo / hypercoagulable state

• hemophilia• dilutional coagulopathy• rare coagulation disorders anticoagulation tx• coagulation problems with liver transplantation

Thromboelastogram(TEG)

Bleeding time

• monitors platelet function

• not specific indicator of platelet function

• not very reliable

• very operator - dependent

• variable from each institution

Bleeding time

• other factors: degree of venostasis, depth and

direction of incision

• no evidence as

• a predictor of risk of hemorrhage

• useful indicator of efficacy of antiplatelet therapy

• insensitive to mild platelet defects

LABORATORY TEST

COMPONENTS MEASUREDNORMAL VALUES

Bleeding time platelet functionvascular integrity

3 - 10 mins

PT I, II, V, VII, IX, X 12 - 14 secs

PTT I, II, V, VIII, IX, X, XI, XII 24 - 35 secs

Thrombin time I, II 12 - 20 secs

Drugs affecting Coagulation

HEMOSTATIC PROCESS AFFECTED

CLASS OF DRUGS

SPECIFIC DRUGS

1º platelet plug formation inhibition

antiplatelet drugs reversible: NSAIDirreversible: ASA

coagulation cascade

IV anticoagulants

oral anticoagulants

standard and LMW heparinswarfarin

fibrinolysis fibrinolytic agents StreptokinaseUrokinaset-PA

Prostaglandin Synthesis

arachidonic acid cyclooxygenase

prostaglandin G2

peroxidase

prostaglandin H2

prostacyclin thromboxane

synthetase synthetase

prostacyclin thromboxane A2

PG F1a thromboxane B2

Mechanism of ActionASPIRIN

arachidonic acid ASPIRIN cyclooxygenase

prostaglandin G2

peroxidase

prostaglandin H2

prostacyclin thromboxane

synthetase synthetase

prostacyclin thromboxane A2

PG F1a thromboxane B2

Mechanism of ActionASPIRIN and NSAIDS

arachidonic acid ASPIRIN cyclooxygenase

prostaglandin G2 NSAIDS

peroxidase

prostaglandin H2

prostacyclin thromboxane

synthetase synthetase

prostacyclin thromboxane A2

PG F1a thromboxane B2

Platelet count

Bleeding time

APTI Prothrom-bin

Presumptive diagnosis

Decreased Prolonged Norm. Norm. Thrombocytopenia

Norm. Prolonged Prolonged Norm. von Willebrand’s disease

Norm./ increased

Prolonged Norm. Norm. Thrombocytopathia

Norm. Norm. Prolonged Norm. „intrinsic” pathway abnormality (FVIII. IX. XI. XII)

Norm. Norm. Norm. Prolonged „extrinsic”pathway abnormality (FVII)

Norm. Norm. Prolonged Prolonged „common” pathway abnorm. (FI. II. V. X.)

Norm. Norm. Norm. Norm. - /FXIII deficiency/ milde bleeding disorder

Diagnosis of bleeding disorders by the screening tests

Antiplatelet Medications

DRUGSITE OFACTION ROUT

E

PLASMA t 1/2

META-BOLISM

Ø PRIORPROCEDURE

↑ PT / PTT

ANTI – DOTE

Aspirin COX 1and 2

oral 20 min hepatic

7 days No/No none

Dipyrida-mole

adenosine

oral 40 min hepatic

24 hrs No/No none

Clopidogrel (Plavix)

ADP oral 7 hrs hepatic

5 days No/No none

Ticlodipine (Ticlid)

ADP oral 4 days hepatic

10 days No/No none

Abciximab (ReoPro)

GPIIb-IIIa IV 30 min renal 72 hrs No/No none

Eptifibatide

GPIIb-IIIa IV 2.5 hrs

renal 24 hrs No/No none

Tiroban GPIIb-IIIa IV 2 hrs renal 24 hrs No/No hemo-dialysis

Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30.

Non-steroidal Anti-inflammatory Medications

DRUGSITE OFACTION ROUT

E

PLASMA t 1/2

META-BOLISM

Ø PRIORPROCEDURE

↑ PT / PTT

ANTI – DOTE

Piroxicam COX 1 & 2

oral 50 hrs hepatic 10 days No/No none

Indome – thacin

COX 1 & 2

oral/ supp

5 hrs hepatic 48 hrs No/No none

Ketorolac COX 1 & 2

oral / IV

5-7 hrs

hepatic 48 hrs No/No none

Ibuprofen COX 1 & 2

oral 2 hrs hepatic 24 hrs No/No none

naproxen COX 1 & 2

oral 13 hrs hepatic 48 hrs No/No none

Diclofenac

COX 1 & 2

oral 2 hrs hepatic 24 hrs No/No none

Celecoxib COX 2 oral 10-17 hrs

hepatic none No/No noneRoberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30.

Anticoagulants & Thrombolytics

DRUG SITE OF ACTION

ROUTE

PLASMA t 1/2

EXCRE- TION

Ø PRIORPROCEDURE

↑ PT / PTT

ANTI – DOTE

Unfraction-ated heparin

IIa/Xa IV/SC 1.5 hrs hepatic

6 hrs No/ Yes

protamine

LMWHs Xa IIIa

SC 4.5 hrs renal 12-24 hrs No/No protamine(partial)

Strepto - kinase

plasmi – nogen

IV 23 mins

hepatic

3 hrs Yes/ Yes

antifibri-nolytics

t-PA plasmi – nogen

IV <5 min hepatic

1 hr Yes/ Yes

antifibri-nolytics

OralAnticoagu- lants

vit-K dep.factors

Oral 2-4days

hepatic

2-4 days Yes/No

Vit. K, rFVIIaPlasma, Prothrom. complex conc.

Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30.

Other Anticoagulants

DRUGSITE OFACTION

ROUTE

PLASMA t 1/2

META-BOLISM

Ø PRIORPROCEDURE

↑ PT/ PTT

ANTI – DOTE

Pentasac- charide

Xa IV 14-17 hrs

renal 4 days No/No rFVIIa?

Bivalirudin IIa IV 25 min hepatic 2-3 hrs Yes/Yes

None

Argatroban IIa IV 45 min hepatic 4-6hrs* Yes/Yes

None

Hirudin IIa IV 1.5 hr renal 8 hrs* Yes/Yes

PMMA dialysis

Activated Protein C (APC)

Va/ VIIIa

IV 2 hrs hepatic 12 hrs No/Yes

none

Ximelagatran

IIa IV 3 hrs renal 24 hrs Yes/Yes

none

PMMA= polymethyl-methyl acrylate*Argatroban &lepirudin may ↑ the normal PT 4-5 secs

Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30.

Bleeding time

• Measure of efficiency of vascular or platelet phases.

• Do not discriminate between vascular defects , thrombocytopenia or platelets dysfunction.

• Not reproducible.• Not a screening test .• normal bleeding time do not exclude a

bleeding disorder- american society of clinical pathologists.

Platelets function assays

• Platelets aggregation using platelets rich plasma.- standard method.

• Nephelometric or photometric measurements.• ADP- produce platelets aggregation directly

irrespective of release of ADP from platelets.• RISTOCETIN- antibiotic that induce platelets

aggregation in presence of von Willebrand factor.• Collagen, epinephrin, thrombin- cause platelet

aggregation by release reaction.

D-DIMERS and FDP:• FDP results from proteolytic cleavage of fibrin by

plasmin. • Increased in DIC and fibrinolysis.• RA factor or residual fibringen may yield false

positive results.• D-DIMER- specific fibrin degradation product.• DDE- TRIMER.• UN POLYMERISED FIBRIN MONOMER.

• UREA CLOT LYSIS ASSAY:• FACTOR XIII assay.• XIII Stabilises fibrin.• Deficiency leads to premature clot lysis.• Screening test. Abnormal results should be

confirmed by quantitative measurements of XIII.

FIVE DRUGS THAT INTERFERE WITH HEMOSTASIS

ASPIRIN ANTICOAGULANTS ANTIBIOTICS ALCOHOL ANTICANCER

Laboratory Evaluation of the Coagulation Pathways

Partial Thromboplastin Time(PTT)

Prothrombin time(PT)

Intrinsic pathway Extrinsic pathway

Common pathwayThrombin timeThrombin

Surface activating agent (Ellagic acid, kaolin)PhospholipidCalcium

Thromboplastin Tissue factor Phospholipid

Calcium

Fibrin clotFibrin Clot

Initial Evaluation of a Bleeding Patient - 1

Normal PTNormal PTT

Consider evaluating for: Mild factor deficiency Monoclonal gammopathy Abnormal fibrinolysis Platelet disorder (a2 anti-plasmin def) Vascular disorder Elevated FDPs

Ureasolubility

Normal

Abnormal Factor XIII

deficiency

Initial Evaluation of a Bleeding Patient - 2

Normal PT

Abnormal PTT

Test for factor deficiency: Isolated deficiency in intrinsic pathway (factors VIII, IX, XI) Multiple factor deficiencies (rare)

Repeatwith

50:50mix

50:50 mix is normal

50:50 mix is abnormalTest for inhibitor activity:

Specific factors: VIII,IX, XI Non-specific (anti-phospholipid Ab)

Initial Evaluation of a Bleeding Patient - 3

Abnormal PTNormal PTT

Test for factor deficiency: Isolated deficiency of factor VII (rare) Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC)

Repeatwith

50:50mix

50:50 mix is normal

50:50 mix is abnormalTest for inhibitor activity:

Specific: Factor VII (rare) Non-specific: Anti-phospholipid (rare)

Initial Evaluation of a Bleeding Patient - 4

Abnormal PT

Abnormal PTT

Test for factor deficiency: Isolated deficiency in common pathway: Factors V, X, Prothrombin, Fibrinogen Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC)

Repeatwith

50:50mix

50:50 mix is normal

50:50 mix is

abnormalTest for inhibitor activity: Specific : Factors V, X, Prothrombin, fibrinogen (rare) Non-specific: anti-phospholipid (common)

Laboratory Evaluation of BleedingOverview

CBC and smear Platelet count ThrombocytopeniaRBC and platelet morphology TTP, DIC, etc.

Coagulation Prothrombin time Extrinsic/common pathwaysPartial thromboplastin time Intrinsic/common pathwaysCoagulation factor assays Specific factor deficiencies50:50 mix Inhibitors (e.g., antibodies)Fibrinogen assay Decreased fibrinogenThrombin time Qualitative/quantitative

fibrinogen defectsFDPs or D-dimer Fibrinolysis (DIC)

Platelet function von Willebrand factor vWDBleeding time In vivo test (non-specific)Platelet function analyzer (PFA) Qualitative platelet disorders

and vWDPlatelet function tests Qualitative platelet disorders

Liver Disease

Decreased synthesis of II, VII, IX, X, XI, and fibrinogen

Prolongation of PT, aPTT and Thrombin Time

Often complicated byGastritis, esophageal varices, DIC

Lab Results in Hemophilia, VWD and Vit K Def

Haemophilia V W Disease Vit K Deficiency

Bleeding Time Normal Increased Normal

PT Normal Normal Increased

APTT Increased + Increased ± Increased

V111 levels Decreased ++ Decreased Normal

vWF levels Normal Decreased Normal

Hemophilia A Hemophilia B Von Willebrand Disease

Inheritance X linked X linked Autosomal dominant

Factor deficiency VIII IV VWFBleeding site(s) Muscle,joint

SurgicalMuscle ,joint Mucous

SkinProthrombin time Normal Normal NormalActivated PTT Prolonged Prolonged ProlongedBleeding time Normal Normal Prolonged or

normalFactor VIII Low Normal NormalVWF Normal Normal LowFactor IX Normal Low NormalPlatelet aggregation Normal Normal Normal

Summary

Symptom Platelet Coagulation Petechiae Yes No

Sites Skin & Mucosa

Deep Tissue

Time Immediate Delayed

Ecchymoses/Hematomas

Yes Yes

Summary Hemostatic Disorders BT Plt PT PTT Vascular Dis - - - -

PLT Disorder - - - -

Factor 8/9 *Congenital - - -

Vit K / Liver*Acquired - - -

Combined (DIC) -

2 year old boy had a fall from chair. He developed swelling of right shoulder and upper arm.

On examination at a hospital the boy had a hematoma of the right shoulder.

There was no previous h/o surgeries, trauma or medication.

Following aspiration of hematoma the patient developed profuse bleeding.

His mother said that the boy’s cousin had a similar bleeding problem.

Case scenario-1

Investigations :• Hb- 8 gms• Hematocrit- 26%• Platelets- 2 lakhs.• Bleeding time- normal• Coagulation profile:• PT- 12 sec• aPTT- 60 sec• Thrombin time- normal

1.Does the lab data support a diagnosis of bleeding disorder?

2.The tests done shows what type of disorder?3.What confirmatory test should be done ?

questions

Answers:1. it’s a coagulation defect.2. normal platelets, bleeding time. APTT prolonged, with normal PT, THROMBIN TIME.

indicate a intrinsic pathway defect with normal common pathway.

There is a defect in factor VIII, IX, XI, XII.3.Specific factor assay, factor substitution testing.If factor 8

activity < 1% Diagnosis- hemophilia A

Case scenario-1

21 yr man was admitted for hernia surgery. No h/o of any medical illness, bleeding , or drug intake. Family history ?

Investigations: Hb-15 gms Hematocrit-44% platelet count –normal bleeding time-10 mins PT- NORMAL APTT- 55 seconds Repeat APTT was also prolonged. Surgery was postponed for him.

CASE SCENARIO-2

• 1.What coagulation disorder likely to be present?

• 2.what are the other investigations required?• 3.what is the diagnosis if the patient has low

normal factor 8 levels and defective ristosetin induced platelet aggregation?

Questions:

1.Normal PT, prolonged APTT suggest a deficiency of VIII, IX, XI, XII deficiency.

Since deficiency of XI, XII are rare, this can be due to def of VIII, or XI.

2. factor substitution study.Specific factor assay.3. in this factor VIII assay showed 30% activity (n- 50-

150%). This finding and lack of bleeding history show he may not have classic factor viii deficiency.

Further tests showed

Answers-2

• Bleeding time prolonged.• Platelets aggregation decreased.• Factor VIII/ VWF decreased.• the lab findings support a diagnosis of von

willebrand disease

Answer-2

62 year old with abnormal bleeding was admitted for dental surgery. His brother had died of traumatic bleeding following a car accident.

I- AT 7 YEARS following a lymph node resection.II- at 30 years the pt had 3 weeks of bleeding following

dental extraction.At 31 years the pt received blood transfusion before

appendicectomy.At 59 years the pt developed gi bleeding following surgery

for hiatus hernia. He received blood transfusions -4 units.

Case scenario-3

Lab data:Hb-7 gmsHematocrit-23%Platelet count- 4.98 lakhsBleeding time-2minsClotting time-188 mins.APTT- 53 sec( control- 35 sec)PT- 13.8 SEC( control-13 sec).Specific assay for factor VIII, IX Showed factor IX level less

than 5%

• 1.what is the diagnosis?• 2. can the patient safely undergo surgery?

questions

1. hemophilia –B2.yes.He should receive factor IX concentrate rather

than whole blood/.

Answers-3

• 22 year female was being evaluated for menorrhagia. Her menses lasted for 8-12 days. The patient also had several nose bleeds which needed cautery. She also reported that her mother and 2 sisters also had long menstrual periods, and her brother needed transfusion following an appendicectomy.

• On examination the patient was pale and had large bruises in the extremities.

Case scenario-4

Lab data:• Hb-10 gms• Hematocrit-27%• platelet count – 2.5 lakh/cumm.• Bleeding time-7 mins( n- 1to 3 mins)• PT- 11 SEC (control-12 sec)• APTT- 29 sec( control-34 sec)

1.What is the likely abnormality?2.What are the further tests required? 3. what is the most likely diagnosis if the patient

has defective platelet aggregation?

questions

1.Thrombasthenia 2. Platelet function studies 3. the patient had deficient platelet aggregation.

A diagnosis of Glanzmann’s thrombasthenia was made.

Autosmal recessive disorder. Platelet concentrate is needed during

surgeries.

Answers-4

• A woman was admitted in labour in an obstetric ward. Pt had no significant history and examination was normal. The patient had irregular contractions.

• In the delivery room she developed profuse bleeding.

Case-5

• Hb-10 gms• Hematocrit-27%• Platelet count -75000• Bleeding time-10 mins• PT-19 SECONDS- ( control-13 sec).• APTT- 65 sec( control-35 sec)• Thrombin time-30 sec( n- 18-22 sec)• Fibrinogen- 90 mg/dl (200-400 mg/dl)• Fibrin split product- positive

Lab data:

1. what is the probable diagnosis?2. what is the probable etiology?3. will whole blood transfusion repress the

bleeding?

1. the diagnosis is DIC.2. may be due to release of placental tissue in to

maternal circulation triggering the coagulation mechanism. There is evidence of fibrinolysis.

3. transfusions may temporarily help. Heparin may be useful

Answers-5

Platelet count  

Bleeding time  

Partial thromboplastin time  

Prothrombin time  

Condition  

unaffected prolonged prolonged unaffected Von Willebrand disease

unaffected unaffected prolonged prolonged Vitamin K deficiency or Warfarin

unaffected prolonged unaffected unaffected Uremia

unaffected unaffected prolonged unaffected Haemophilia

unaffected unaffected prolonged prolonged Factor V deficiency

unaffected prolonged unaffected unaffected Aspirin

decreased prolonged unaffected unaffected Thrombocytopenia

decreased prolonged prolonged prolonged End-stage Liver failure

decreased prolonged prolonged prolonged Disseminated intravascular coagulation

decreased prolonged unaffected unaffected Bernard-Soulier syndrome

Functions of the Liver

Most clotting Factors are produced in the liver

Factor Name Roman Numeral Source Fibrinogen I Liver Prothrombin II Liver * * Tissue Factor III Damages cells Calcium IV Gut and bone Preaccelerin V Liver and platelet Proconvertin VII Liver * * Antihemophilic Factor VIII Platelets and endothelium

Christmas Factor IX Liver * * Stuart-Prower Factor X Liver * * Plasma thromboplastin antecedent XI Liver Hageman Factor XII Liver Fibrin-stabilizing Factor XIII Liver

* * Dependent on vitamin K for synthesis in liver

Microsoft clipart

Nowak, T.J., Handford, G. A. (2004). Pathophysiology: Concepts and Applications for Health Care Professionals. (3rd Ed). McGraw-Hill. NY

Which of these Factors is not synthesized in the liver?

a) Prothrombin (Factor II)

b) Antihemophilic Factor (Factor VIII)

c) Hageman Factor (Factor XII)

d) Stuart-Prower Factor (Factor X)

X Incorrect

X No

X Try Again

CorrectSource: Platelets and endothelium

Click on the correct response:

What happens if the Liver is Damaged?

So the well equipped guy comes

PLATELETS• They have receptors• They provide a phospholipid surface…• They contain granules

Dense - serotonin , ADP , Ca++

Alpha - coagulation factors , vWF , PDGF

Endothelial damage:Platelet plug formation

• Endothelial damage exposure to collagen:– Promotes platelet adherence and activation– Activated platelets secrete ADP and TxA2

• ADP promotes platelet recruitment• TxA2 promotes platelet aggregation

– Result: formation of platelet plug (white clot)

No one can hide the insults from them……

• A D H E S I O N – [ v W F ]

• S E C R E T I O N - [ T x A 2 , A D P ]

• A G G R E G AT I O N

L e a d s t o P R I M A R Y H E M O S T A S I S

Leads to….

PRIMARY HEMOSTASIS

• Occurs within SECONDS

The balancing act

• PG E2 • PG I2 • NO ……..

all these oppose TxA2 & ADP

In need of…. FIBRIN

• The linking of platelets in the primary plug, by fibrin, converts it into a definitive clot. This requires the participation of the Coagulation Cascade. This process is known as SECONDARY HEMOSTASIS

In need of…. FIBRIN

• The linking of platelets in the primary plug, by fibrin, converts it into a definitive clot. This requires the participation of the Coagulation Cascade. This process is known as SECONDARY HEMOSTASIS

• Thrombin generation: the pivotal point of the coagulation process

• Thrombin actions:– Activates FXI, amplifying

thrombin generation– Converts fibrinogen to

fibrin– Activates FXIII– Activates platelets

• Result: RED CLOT

Thrombin generation to fibrin-platelet clot formation

Cascade vs. cell-based model

Cell-based model• Hemostasis represented as:

• Occurring on two cell surfaces • Tissue factor bearing cells• Platelets

• Three overlapping phases:• Initiation (TF bearing cells)• Amplification (platelets)• Propagation (platelets)

• The coagulation cascades are still important, but are cell-based• The extrinsic pathway works on the

surface of the tissue factor bearing cells• The intrinsic pathway works on the

surface of platelets• Routine coagulation tests do not represent

the cell-based model of hemostasis.

Tissue factorbearing cells 1. Initiation

Platelets

Activated platelets

2. Amplification

3. Propagation

IIa

IIa

Clot:The end product of hemostasis