This document discusses coagulation disorders and bleeding disorders. It describes the normal hemostatic mechanisms including the vascular, platelet and coagulation systems. Bleeding disorders can cause spontaneous or excessive bleeding and can be due to increased vascular fragility, platelet deficiencies or dysfunctions, or derangements of clotting factors. Specific disorders discussed include hemophilia A/B, von Willebrand's disease, and disseminated intravascular coagulation. Laboratory tests that can identify coagulation disorders include the tourniquet test, bleeding time, clotting time, platelet count, clot retraction time, prothrombin time, activated partial thromboplastin time, and thrombin time. Further specific tests may

1. COAGULATION DISORDERSby: Noel C. Santos, M.D.

2. HemostasisPhysiologic mechanisms to protect from blood loss.Stops bleeding from an injured siteMaintains blood in the fluid state within the vascular compartmentHEMORRHAGETHROMBOSIS

3. Normal Hemostatic MechanismsVASCULAR SYSTEMPLATELETSCOAGULATION SYSTEMIntrinsic PathwayVIII, vWF, IX, XI, XII, prekallikrein, HMWKExtrinsic PathwayIII, VIICommon PathwayFIBRINOLYTIC SYSTEM

4. Primary Phase – formation of platelet plugsSecondary Phase – formation of fibrin plugs

5. Bleeding DisordersSPONTANEOUS - petechiae, purpura, mucous membranes, GI bleeding, hematuria, into joint spacesEXCESSIVE - after trauma or surgery- range is from lethal diseases (factor VIII deficiency, Bernard-Soulier's, Glanzmann's) to asymptomatic (factor XII deficiency, many von Willebrand's)

6. INCREASED VASCULAR FRAGILITYseldom seriousskin bruises, dependent petechiae, gum bleeding, hematuria, nosebleeds, GI bleeds. Infections - damage endothelium AmyloidosisCollagen problemsImmune-complex deposition in vessel walls

7. PLATELETS DEFICIENCY or DYSFUNCTIONapparent immediately after trauma (petechiae – skin & mucus membranes)Thrombocytopeniacount is less than 100 x 109/literbleeding after trauma = platelet count is below 40 x 109/literspontaneous bleeding = count is below 20 x 109/liter (petechiae &purpura randomly over the skin, blood blisters in the mouth, GI, GU, CNS bleeding.)severe spontaneous bleeding = when count gets < 10 x 109/liter

13. ThrombocytopeniaCauses:Decreased productionDecreased survivalSequestrationDilutionalIncreased utilization

20. Defective platelet functionsCongenitalAdhesion (Bernard-Soulier syndrome)Aggregation (thrombasthenia - Glanzmann’s)SecretionAcquiredAspirin ingestionUremia

21. DERANGEMENTS OF CLOTTING FACTORSapparent only few minutes after traumadeficiency can be mild or severeabsent or defective or the deficiency may be due to an inhibitor against ithereditary (single) or acquired (several)ecchymoses or hematomas after minor injury, bleeding for days after tooth extractions, or bleeding into joint spaces (hemarthroses)

23. HemophiliaHemophilia A – deficient Factor VIIISex-linkedlevels less than 1% of normalHemophilia B – deficient Factor IX (Christmas disease)Sex-linkedAssay of corresponding factor/s

24. Von Willebrand’s DiseaseAutosomal dominantType I – most common, inhibited release of multimers by unknown mechanisms, less amount is availableType II – defective multimers are releasedType III – none is producedUsually associated with reduced Factor VIII

25. FIBRINOLYTIC ProblemsExcessive plasminogen activationElevated fibrin degradation productsDISSEMINATED INTRAVASCULAR COAGULATIONThrombohemorrhagic disorderSECONDARY COMPLICATIONactivation of coagulation sequencemicrothrombi formation with consumption of platelets, fibrin & coagulation factorsactivation of fibrinolytic mechanisms

26. DISSEMINATED INTRAVASCULAR COAGULATIONsigns and symptoms relating to infarctionhemorrhagic diathesis due to depletion of platelets and clotting factors AND activation of fibrinolytic mechanismsMechanisms:release of tissue factor and thromboplastic substances into the circulationendothelial injury

27. HYPERCOAGULABLE BLOOD – Thrombosis"Thrombophilia“, "hypercoagulopathy“Not rare, but tends to get overlooked.deficient natural anticoagulants (Protein C, Protein S and Antithrombin III)Sticky platelet syndromeDysfibrinogenemia - mutant fibrin is not removed by plasminplasminogen deficiency

29. Laboratory Screening TestsPrimary Phase – Bleeding TimeSecondary Phase – Clotting Time

30. Laboratory Screening TestsVASCULAR SYSTEM – capillary fragility testing (tourniquet test)PLATELETS – count and function (CRT)COAGULATION SYSTEMIntrinsic Pathway – APTTExtrinsic Pathway – Prothrombin timeCommon Pathway – Thrombin timeFIBRINOLYTIC SYSTEM – FDP, antithrombin, natural anticoagulants

31. Laboratory Tests – SPECIFICPlatelet Function TestsAssays of Clotting Factors and AnticoagulantsDetections of antibodies against coagulation elements

32. SUMMARYTourniquet Tests – (+) or (-)Bleeding Time – (N) or (P)Clotting Time – (N) or (P)Platelet Count – (N) or Dec or IncClot Retraction Time – (N) or AbnProthrombin Time – (N) or (P)Activated Partial Thromboplastin Time – (N) or (P)Thrombin Time – (N) or (P)What Specific Tests?

33. COAGULATION DISORDERSby: Noel C. Santos, M.D.