BLEEDING DISORDERS

HEMOSTASIS-1 In health hemostasis ensures that the blood remains fluid and contained in the vasc.system. If a vessel wall is damaged,a number of mechanisms are activated promptly to limit bleeding,involving: 1-Endothelial cells. 2-Platelets. 3-Plasma coag.factors. 4-Fibrinolytic system.

HEMOSTASIS-2 These activities are finely balanced between keeping the blood fluid and preventing intravasc.thrombosis. 1-Pimary hemostasis: vasoconstriction and platelet adhesion and aggregation leading to the formation of the platelet plug. 2-Secondary hemostasis: involves activation of coagulation system leading to the generation of fibrin strands and reinforce the platelet plug. 3-Fibrinolysis: activation of fibrin-bound plasminogen resulting in clot lysis.

ROLE OF ENDOTHELIAL CELLS IN HEMOSTASIS Blood vessels are lined with endothelial cells,which synthesize and secrete various agents,that regulate hemostasis. 1-Procoagulant(prothrombotic) agents:tissue factor,von Willebrand factor,F V ,F VIII. 2-Anticoagulant (antithrombotic) agents: prostacyclin,nitric oxide,endothelin-1.

ROLE OF PLATELETS IN HEMOSTASIS Each megacaryocyte produces 1000-2000 platelets. remain in the circulation for about 10 days. Activated platelets release the contents of stored granules into the blood plasma. The granules include, serotonin, platelet-activating factor (PAF), vWF, platelet factor 4, and thromboxane A2 , which, in turn, activate additional platelets Platelet adhesion. Platelet aggregation.

COAGULATION SYSTEM Coag.factors: are plasma proteins synthesized in the liver which when activated lead to the deposition of fibrin. 1-Initiation phase: leads to the formation of the complex TF-VIIa. 2-Amplification phase: leads to the formation of a small amount of thrombin from prothrombin. 3-Propagation phase:leads to the formation of much larger amounts of fibrin.

Coagulation cascade Intrinsic system (surface contact) Extrinsic system (tissue damage) XII XIIa Tissue factor XI XIa IX IXa VIIa VII VIII VIIIa Vitamin K dependant factors X Xa V Va II IIa IIa (Thrombin) Fibrinogen Fibrin

INHIBITORS OF COAGULATION Are proteins that inhibit activated procaogulation enzymes and prevent excessive intravasccular coagulation Raised levels are not associated with bleeding. Reduced levels may predispose to thrombosis. Antithrombin. Protein C,Protein S. Tissue Factor Pathway Inhibitor (TFPI).

FIBRINOLYSIS Plasminogen Plasmin Fibrin FDPs Small amouns of fibrin are constantly deposited within the vascular system and are removed by the fibrinolytic system. Fibrinolysis is the process wherein a fibrin clot, the product of coaglation, is broken down. Plasminogen Plasmin Fibrin FDPs

HISTORY 1-Site of bleeding. 2-Duration of bleeding. 3-Precipitating cause. 4-Surgery. 5-Family history. 6-Systemic illnesses. 7-Drugs.

Clinical Features of Bleeding Disorders Platelet Coagulation disorders factor disorders Site of bleeding Skin Deep in soft tissues Mucous membranes (joints, muscles) (epistaxis, gum, vaginal, GI tract) 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

Coagulation factor disorders Inherited bleeding disorders Hemophilia A and B vonWillebrand disease Other factor deficiencies Acquired bleeding disorders Liver disease Vitamin K deficiency/warfarin overdose DIC

Hemophilia A and B Hemophilia A Hemophilia B Coagulation factor deficiency Factor VIII Factor IX Inheritance X-linked X-linked recessive recessive Incidence 1/10,000 males 1/50,000 males Severity Related to factor level <1% - Severe - spontaneous bleeding 1-5% - Moderate - bleeding with mild injury 5-25% - Mild - bleeding with surgery or trauma Complications Soft tissue bleeding

Clinical manifestations hemophilia A & B are indistinguishable clinically Hemarthrosis (most common) Fixed joints Soft tissue hematomas (e.g., muscle) Muscle atrophy Shortened tendons Other sites of bleeding Urinary tract CNS, neck (may be life-threatening) Prolonged bleeding after surgery or dental extractions

Disseminated Intravascular Coagulation (DIC) Is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood vessels throughout the body. As the small clots consume coagulation proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs. The small clots also disrupt normal blood flow to body organs which may malfunction as a result .

Depletion of platelets and coagulation factors Systemic activation of coagulation Depletion of platelets and coagulation factors Intravascular deposition of fibrin Thrombosis of small and midsize vessels with organ failure Bleeding

Common Clinical conditions associated with DIC Sepsis Trauma Head injury Fat embolism Malignancy Obstetrical complications Amniotic fluid embolism Abruptio placentae Reaction to toxin (e.g. snake venom, drugs) Immunologic disorders Severe allergic reaction Transplant rejection

Classification of platelet disorders Qualitative disorders Inherited disorders (rare) Acquired disorders Medications Chronic renal failure Cardiopulmonary bypass Quantitative disorders Abnormal distribution Dilution effect Decreased production Increased destruction