Coagulation failure in pregnancy Dr : Hashmi Hajrai MBBCh, DGO, M’MAS, MRCOG Consultant Obstetrician & Gynaecologist

Learning objectives The student should understand the alterations in coagulations & fibrinolysis associated with pregnancy Refresh his mind about the normal coagulation cascade mechanisms and its triggers Broad line classification of coagulation failure in pregnancy

Understanding the pathogenesis of DIC syndrome, diagnosis, complications & management outlines Brief knowledge on some other important causes of coagulation failure in pregnancy

Coagulations changes in pregnancy Bleeding during labour is dealt with effectively by - increased production of coagulation factors during pregnancy - increased blood volume - myometrial contraction

this hypercoagulable state with local activation of clotting system is associated with increased risk of not only VTE but also DIC

The fibrinolytic system is responsible for disposing of fibrin after fulfilling its haemostatic function Plasma proteases are responsible for controlling the speed and extent of coagulation & fibrinolysis

Hemostasis is a balancing act between clot formation and fibrinolysis or clot dissolution.

HEMOSTASIS Primary + Secondary + Tertiary Primary Hemostasis Platelet Plug Formation:dependent on normal platelet number & function Secondary Hemostasis Activation of Clotting Cascade  Deposition & Stabilization of Fibrin Tertiary Hemostasis Dissolution of Fibrin Clot:dependent on Plasminogen Activation

Normal Artery Endothelium Smooth Muscle Adventitia

Vascular Damage

Hemostasis

Overview of blood coagulation

Second step is activation of coagulation Three phases Intrinsic pathway Extrinsic pathway Common pathway

Coagulation cascade thrombin fibrin X Intrinsic pathway XII XI Extrinsic pathway IX APTT VII VIII X PT thrombin Prothrombin (II) V, Ca, P/L fibrin fibrinogen XIII STABILISED FIBRIN

Thrombin converts fibrinogen to fibrin monomer by initially cleaving fibrinopeptides A and B. After a loosely cross-linked fibrin clot is formed, FXIIIa is able to cross-link fibrin, leading to clot stabilization.

The process of fibrinolysis enables cross-linked clots to be degraded The process of fibrinolysis enables cross-linked clots to be degraded. The fibrinolytic process involves the zymogen plasminogen, which is converted to plasmin by tPA or uPA. PAI-1 and 2-antiplasmin are the physiologic inhibitors of plasminogen activator and plasmin, respectively.

Classification of coagulation disorders Congenital coagulation failure disorders these are uncommon.....examples: Von Willebrand’s disease...will be discussed Haemophilia A & B

Acquired coagulation failure disorders are far more commonly seen Thrombocytopenic coagulopathies Disseminated intravascular coagulation ..DIC Anticoagulant therapy

4. Congenital Coagulopathies Von Willebrand disease Factor synthesized by endothelial cells & megakaryocytes Forms a complex with factor VIII Mediates platelet adhesion and collagen Inherited as autosomal dominant trait

Congenital Coagulopathies Von Willebrand disease During pregnancy Prophylactic treatment factor VIII level below 25% DDAVP is administered as labor begins – repeated every 12 hrs. FFP or cryoprecipitate (500-1,500 units of factor VIII activity)

Congenital Coagulopathies Von Willebrand disease During labor Factor VIII levels should be maintained at 50% of normal CS – factor VIII level to 80%of normal Check daily during the post partum period

Congenital Coagulopathies Other coagulation factor deficiencies Factor VIII ( hemophilia A) Factor IX ( hemophilia B)

Thrombocytopenic Coagulopathies Autoimmune Thrombocytopenic Purpura Idiopathic thrombocytopenic purpura Immunoglobulin G (IgG)

Thrombocytopenic Coagulopathies Diagnosis Platelet count < 100,000/mm3 Increased numbers of megakaryocytes Increased platelet volume Diameter

Thrombocytopenic Coagulopathies treatment Conservative management Corticosteriods – if platelet count <20,000/mm3 before the onset of labor or < 50,000/mm3 at time of delivery High dose IV immunoglobulin produces increase in platelet count Significant hemorrhage – immediate postpartum period platelet transfusion

The theoretical risk of intracranial haemorrhage in the thrombocytopenic foetus has not been shown to be reduced by C/S therefore C/S should be performed for obstetric reasons

DIC SYSTEMIC ACTIVATION OF COAGULATION An acquired syndrome characterized by systemic intravascular coagulation Coagulation is always the initial event Intravascular deposition of fibrin Depletion of platelets and coagulation factors Thrombosis of small and midsize vessels Bleeding DEATH Organ failure

Obstetric causes of DIC Falls into three categories conditions associated with release of tissue thromboplastin that activates extrinsic pathway - placental abruption - dead foetus - molar pregnancy Conditions associated with endothelial damage leading to activation of intrinsic & extrinsic pathways - pre- eclampsia & eclampsia

Conditions having non-specific or indirect action - amniotic fluid embolism - gram negative septicaemia - saline abortion

Mechanism of DIC Bick et al., 2002

Clinical manifestation of DIC Those of the underlying cause Those due to Complications of DIC

Haemorrhagic manifestations Involving skin & mucus membranes Ecchymosis Petechiae Bleeding from the gum Haematuria GIT bleeding Venepunctur oozing Intracranial or intracerebral haemorrhage

Thrombotic manifestations Neurologic with multifocal lesions , delirium & coma Dermatologic with focal ischaemia & superficial gangreen Renal with cortical necrosis and ureamia GIT acute ulceration with bleeding Vascular occlusion causing pulmonary infarction or peripheral vascular gangreen

Lab results Markedly decreased platelet count Markedly Increased fibrin degradation products FDP’s Fragmented RBCs & microspherocytes in peripheral blood film Low fibrinogen , factor II , V & VII Prolonged PT, PTT & TT

Microscopic findings in DIC Fragments Schistocytes Paucity of platelets

Fragmented RBC T. TATU ๓ ธันวาคม ๒๕๕๑

Treatment of DIC Remove underlying cause Replenish depleted factors FFP Provides source of most factors Cryoprecipitate provides fibrinogen Platelet and blood support Cautious use of heparin Up to date, emedicine

conclusion Blood coagulation is a major component of haemostasis. Increased Coagulation factors levels in pregnancy is meant to minimize blood loss at time of delivery This haemostatic mechanism could fail risking patient’s life

Thrombocytopenic coagulation failure and DIC syndrome are the most commonly seen in obstetric practice Congenital causes of coagulation failure are uncommon and usually already diagnosed prior to pregnancy DIC syndrome is always secondary to an underlying pathology

If diagnosis of DIC is missed or appropriate action is delayed it can cause serious maternal morbidity or even death Platelet transfusion and coagulation factor replacement or fresh blood transfusion are the main stay of treatment besides other supportive therapy

Use of heparin is controversial Use of heparin is controversial . Haematologist opinion should be sought before it’s use