Gus DekkerLyell McEwin Hospital, University of AdelaideOBSTETRIC DIC

DIC in placental abruption first described by De Lee in 1901 as temporary haemophilia

introduction

stasisvessel damagehypercoagulabilityVirchows Triad

Haemostatic System and Pregnancy

Blood flow of 700 ml/minute has to be staunched within seconds, myometrial contraction plays a vital role in securing haemostasis. Rapid closure of the terminal part of the spiral artery will be further facilitated by removal of the elastic lamina

The placental site is rapidly covered by a fibrin mesh following delivery. The increased levels of fibrinogen and other coagulation factors will be advantageous to meet the sudden demand for haemostatic components

Haemostatic System and Pregnancyhypercoagulable state vulnerable to a spectrum of disorders ranging from VTE to DICDIC always secondary to a trigger such as placental abruption or AFE due to release of thromboplastic intravascularly or endothelial cell injury resulting from sepsis or severe preeclampsiaOutcome depends primarily on our ability to deal with the trigger and not on direct attempts to correct the coagulation deficit

haemostasis

DIC

DIC and specific obstetrical disorders

PPH and 4 TsThe traditional pneumonics 4Ts: tone, tissues, trauma and thrombin can be used to remember the potential causes.

Massive PPH may be caused by one or more causes and PPH from any cause will result in coagulopathy

ToneUterine atony rapid and severe PPH, hypovolemic shock and secondary DIC. Risk factors for uterine atony antenatal: uterine over distension related to multiple pregnancy, polyhydramniosIntrapartum: precipitous labour, prolonged labour, augmentation of labour with oxytocin and intrapartum placenta abruption, AFEActive management of 3rd stage best prophylaxis

Tissue, Trauma and ThrombinTissueRPOC are more common after vaginal deliveryBleeding from placenta praevia or placenta accreta often encountered during LSCSTraumaTrauma-related bleeding can be caused by lacerations of genital tract or uterine rupture

Thrombin

Haematological management of the bleeding obstetric patientAcute and frightening problemProtocol team approach haematologist, anaesthetist, obstetrician, midwifery staffEducation, regular drills and adherence to guidelines and protocols are important to reduce haemorrhage-related maternal deathsFind the source of bleeding ongoing haemorrhage will trigger shock and DIC

Management severe haemorrhage Prompt and adequate fluid replacementavoids renal shutdownliver be able to rapidly clear FPDs !Simple crystalloids Hartmann, Ringer lactate 2-3 x estimated blood lossArtificial colloids bovine gelatin-polygeline (iso-oncotic, room temperature, long shelf-life, improves renal function, non-immunogenicDo not use Dextrans

Management severe haemorrhage Whole blood treatment of choice in obstetric coagulations failures but not available, risk transmission infectionsFFP contains all clotting factors in plasma (stored at -30 well preserved for 1 yr)Occasionally fibrinogen (4 gram) will increase fibrinogen with 1 g/L (haematologist)Platelets rarely needed (persistent bleeding with platelets < 20.000 indication)RPC in case or urgency unmatched; blood group unknown O neg (? In Indonesia)

Management severe haemorrhage Each unit of RBC increases Hb by 1 g/dl and haematocrit by 3%

Start RBC transfusion is clinical decision

In massive PPH scenarios start with ordering at least 6 units (massive blood loss protocol)

First Hb results are not reliable anyway

Management severe haemorrhage If you only give RPC create deficiency of labile factors like V, VIII and plateletsIn case of major obstetric haemorrhage !1 FFP per 1 RPC, 1 g calcium gluconate after 4 RPC If possible achieve vaginal birthMaintain uterine contraction !Consider alternative approaches for persisting local bleeding (arterial embolization, Bakri, B-Lynch suture etc)

Emergency laboratory assessment haemostasisDo not take specimen from indwelling lineRapid screening tests: aPTT, INR, thrombin time (TT) , fibrinogen, D-dimerTT estimation of the thrombin clottable fibrinogen (citrate plasma sample) most valuable overall rapid screen (normal 10-15 sec)TT prolonged with depleted fibrinogen and increased FDPs

ResuscitationABCGET HELP Code Blue ObstetricIV access 2 large-bore cannulasFoley catheter; fluid balance, scribeShock index heart rate/SBP Normal 0.5 0.7 > 0.9 intensive treatment required

Still bleeding after initial resuscitation

Examination under anaesthesia

Uterine tamponade

Tamponade test after vaginal birth

Other measuresSelective embolisation (gelatin sponge)

Uterine artery, Internal Iliac ligation, progressive stepwise devascularization

Hysterectomy

rFVIIa boosts thrombin generation on activated platelets

Placental Abruption (PA)Most common obstetric cause of DICSmall abruptions raise FDPs changes D-dimerGreat spectrum severity haemostatic failure10% PA show significant coag abnormalitiesExternal blood loss real blood lossComplete abruption > 2 ltrBlood pressure may give false reassurance (pain, young patients, preeclampsia what is her pulse, respiratory rate and urine output !!!)

Placental Abruption (PA)Signs of DIC oozing puncture site vein, bleeding mucous membranes, epistaxisProlonged TT, low platelets, low fibrinogen, FDPsRestore circulating blood volume ! - FDPs will cause serious PPH & low cardiac outputFDIU - aim is prompt vaginal birth avoiding soft tissue traumaPPH most common cause of death in PA Regional block contraindicated, no NSAID

Placental Abruption (PA)No evidence use heparin (circulation not intact)Consider Trasylol (Aprotinin) or Cyklokapron (Tranexaminic acid 5-15 mg/kg) cases of uterine inertia with high FDPs (risks small vessels blockage)Maintain CVP ICU admissionFactor VIIa 90 mcg/kg IV over 3-5 min can be repeated after 20 min only useful when surgical haemostasis is achieved, no hypothermia , no acidosis, fibrinogen > 1 g/ltr, and platelets > 50

Amniotic Fluid Embolism (AFE)Initial high mortality from cardio-respiratory failure if the mother survives long enough massive DIC will followDifferential diagnosis pulmonary embolism, aspirationObjective of treatment is to sustain circulation while the intravascular thrombus in the lungs is cleared by fibrinolytic system

Low grade DIC

Preeclampsia, HUS, TTP

D-dimer is easiest test and of prognostic value in preeclampsia

Dead fetus syndrome

Dead Fetus SyndromeGradual depletion of clotting factors following IUFD, changes not detectable until after 3-4 weeks

> 5 weeks 30% will develop DIC (rare in Oz)

Correct clotting abnormalities and stop DIC with UFH prior to IOL

Endotoxic Shock and SepsisUsually Gram negative

Endothelial cell damage, secondary RBC intravascular haemolysis (MAHA)

Transfusion has little or no effect

Elimination of the (uterine) infection is the key

Terima Kasih Questions ?

HELLP SYNDROME

Acute Fatty Liver of Pregnancy (AFLP)

Acute Fatty Liver of Pregnancy (AFLP)

Prodromal symptoms for a week before jaundice

Profound haemostatic defect (including very low to undetectable AT) consumption + effects liver failure

Acute Fatty Liver of Pregnancy

AFLP, rare but potentially fatal complication of 3rd trimesterIncidence 1/10,000- 15,000 births. AFLP more common in nulliparous women and women with multifetal gestation

Onset symptoms 27 -40 weeks, average 36 weeks (2nd trimester cases have been reported ) and first onset of signs/symptoms may be postpartum period

Typical patient presents with a 1- to 2-week history of malaise, anorexia, nausea, vomiting, epigastric or right upper quadrant pain, headache, or jaundice. Urine will have a bright yellow appearance

Rarely, patients may present with hepatic encephalopathySymptoms of preterm labor or lack of fetal movement may be the presenting complaint in some of these patients

AFLP physical examination

Physical examination reveals an ill-appearing patient with jaundice

Some patients will have a low-grade fever

Other findings may include hypertension and even proteinuria and ascitesand bleeding from severe coagulopathy

Neurologic findings may range from normal to lethargy, agitation, convulsions, confusion, and even coma (differential diagnosis preeclampsia)

T --BIOCHEMICAL FEATURES OF ACUTE FATTY LIVER OF PREGNANCYModified from Fesenmeier MF, Coppage KH, Lambers DS, et al: Acute fatty liver of pregnancy in 3 tertiary care centers. Am J Obstet Gynecol 192:1416-1419, 2005.

Biochemical FeatureAverage at DiagnosisRange at DiagnosisPeak or NadirAST (

Baha Sibai Seminars in Perinatology 2009

Management of AFLP

Clinical course of AFLP characterized by progressive and sometimes sudden deterioration in maternal and fetal conditions

Admit in HDU/delivery unit

FHRM required concurrent with maternal evaluation

Fetal compromise may be present even in those with stable maternal conditions

Non-reassuring fetal testing may be secondary to maternal acidosis and/or reduced uteroplacental blood flow. The presence of maternal acidosis may be reflected in reduced to- absent fetal movement, absent fetal breathing, or tone during biophysical profile testing

Management of AFLP

Maternal stabilization and delivery, correct coagulopathy

AFLP is not an indication for CS, CS on fetal indication

IOL with an attempt for vaginal delivery within 24 hours is a reasonable approach

Management of AFLP

Avoid epidural analgesia; analgesia during labor can be provided byintermittent use of small doses of systemic opioids

Try to avoid vaginal trauma and lacerations during vaginal delivery

In case of CS general anesthesia. Avoid incisions that require extensive dissection, such as the Pfannenstiel incision. Meticulous attention to secure hemostasis

Midline incision, use a subfascial drain, keep the skin incision open for at least 48 hours to avoid hematoma formation

DIC you never die aloneJ Pritchard AJOG 1976See DIC run and play in the blood vesselsSee JaneSee Jane not run but play and get pregnantJane will now get DIC sinceDIC occurs in preeclampsia/eclampsiaDIC occurs in abruptio placentaeDIC occurs with obstetric complicationsIf Janes baby Dick is asphyxiated, Dick may get DICJane should not have gotten pregnantBut the Pill while preventing Dick, may cause DICBut so can malaria, virus infections, a bad bump on the head,even infectious mononucleosisMore and more it appears most things in life can cause DICProbably no one dies aloneThere is always DIC

Thank You - Questions/Comments ?

Permanent hemostatic plugThe term permanent hemostatic plug is really misleading because, as we'll see later in this lesson, the plugs are not permanent because there is built-in system that begins to dissolve them as soon as they are formed. However, we'll continue to refer to it as "permanent" here, if only because it is a good contrast with the "temporary" plug. The temporary hemostatic plug is formed by platelets. The permanent hemostatic plug is formed when the clotting cascade gets activated and the platelet plug gets made more permanent by the glue known as fibrin. This fibrin clot forms the needed bulk and anchoring mechanism.

In the picture below, there is a platelet plug (temporary) being enmeshed by fibrin (permanent plug).

The clotting cascade consists of a number of clotting factors, most of which are designated by Roman numerals. All of these factors are normally present in blood, however in an inactive form. Hafta be, or we would just be one massive clot alla time. In order for clotting to occur, each one has to get activated. This happens, and in a cascade-like manner, hence the term clotting cascade. The end result is the formation of thrombin (see, I told you we would get to thrombin before long), that acts on fibrinogen to turn it into fibrin. Fibrin is physically a strand-like substance that holds platelets together in the permanent hemostatic plug. Actually, fibrin does much more than this and we will deal with fibrin extensively when we get to the unit on inflammation.There are basically two pathways - extrinsic and intrinsic - in the clotting cascade. The intrinsic pathway gets its start when Larry Hageman factor (also known as Factor XII) contacts a subendothelial surface. The extrinsic pathway gets its start when substances in the tissue contact Factor VII. The extrinsic pathway is faster and gets put into action when the damage is deeper. It augments the intrinsic pathway.

Study this diagram and read through your notes. Other than the diagrams, there are no good visuals to depict this. I don't see much point in reiterating the notes here. READ THEM and KNOW THE CASCADE. Here are some questions that might test your understanding of the cascade:An anticoagulant used for collecting blood for CBC (complete blood count) is EDTA. How does this substance keep the clotting cascade from occurring? When clotting is measured in the laboratory, is it the extrinsic or intrinsic system that is being measured, and why? Surgical trauma acts via which pathway predominantly? Many rodenticides act by tying up Vitamin K so that the rodents bleed to death. Which factors are involved? Next Page

Permanent hemostatic plugThe term permanent hemostatic plug is really misleading because, as we'll see later in this lesson, the plugs are not permanent because there is built-in system that begins to dissolve them as soon as they are formed. However, we'll continue to refer to it as "permanent" here, if only because it is a good contrast with the "temporary" plug. The temporary hemostatic plug is formed by platelets. The permanent hemostatic plug is formed when the clotting cascade gets activated and the platelet plug gets made more permanent by the glue known as fibrin. This fibrin clot forms the needed bulk and anchoring mechanism.

In the picture below, there is a platelet plug (temporary) being enmeshed by fibrin (permanent plug).

The clotting cascade consists of a number of clotting factors, most of which are designated by Roman numerals. All of these factors are normally present in blood, however in an inactive form. Hafta be, or we would just be one massive clot alla time. In order for clotting to occur, each one has to get activated. This happens, and in a cascade-like manner, hence the term clotting cascade. The end result is the formation of thrombin (see, I told you we would get to thrombin before long), that acts on fibrinogen to turn it into fibrin. Fibrin is physically a strand-like substance that holds platelets together in the permanent hemostatic plug. Actually, fibrin does much more than this and we will deal with fibrin extensively when we get to the unit on inflammation.There are basically two pathways - extrinsic and intrinsic - in the clotting cascade. The intrinsic pathway gets its start when Larry Hageman factor (also known as Factor XII) contacts a subendothelial surface. The extrinsic pathway gets its start when substances in the tissue contact Factor VII. The extrinsic pathway is faster and gets put into action when the damage is deeper. It augments the intrinsic pathway.

Study this diagram and read through your notes. Other than the diagrams, there are no good visuals to depict this. I don't see much point in reiterating the notes here. READ THEM and KNOW THE CASCADE. Here are some questions that might test your understanding of the cascade:An anticoagulant used for collecting blood for CBC (complete blood count) is EDTA. How does this substance keep the clotting cascade from occurring? When clotting is measured in the laboratory, is it the extrinsic or intrinsic system that is being measured, and why? Surgical trauma acts via which pathway predominantly? Many rodenticides act by tying up Vitamin K so that the rodents bleed to death. Which factors are involved? Next Page

*Virchow was a 19th century german pathologist who practiced in Berlin. He first described the conditions required for predisposition to development of thrombus.***