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MLAB 1227- Coagulation Keri Brophy -Martinez

MLAB 1227- Coagulation Keri Brophy -Martinez. Coagulation Disorders: Primary Hemostasis. Clinical manifestations of Bleeding Disorders. Type of bleeding indicates which component of the hemostatic system is Defects in primary hemostasis

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MLAB 1227- Coagulation Keri Brophy -Martinez

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  1. MLAB 1227- CoagulationKeri Brophy-Martinez Coagulation Disorders: Primary Hemostasis

  2. Clinical manifestations of Bleeding Disorders • Type of bleeding indicates which component of the hemostatic system is • Defects in primary hemostasis • Easy bruising, petechiae (small dots), purpura (bleeding into the skin), ecchymoses (large superficial hemorrhaging), and spontaneous bleeding, especially from mucosal surfaces • Defects in secondary hemostasis • Prolonged deep bleeding into joints/muscles or hematomas: With these disorders can see spontaneous bleeding (severe factor deficiency) or post-injury (mild factor deficiency) • Combination • Multiple site bleeding occurs in severe combined defects (DIC). Platelet activity and coag proteins are related so disorders of one can affect the other since platelets provide phospholipid binding sites for clotting factor interaction.

  3. A: Petechiae B: Ecchymosis C: Hematoma

  4. Evaluation of Potential Bleeding Disorder • Obtain Medical history • Age of onset • Symptoms • Family history • Drug history • Exposure to toxins • Physical exam • Type and sites of bleeding • Spontaneous/ result of trauma • Order and interpret lab screening tests • Platelet count • PT • PTT • BT or PFA

  5. Vascular System Disorders • Defects may be due to abnormalities in the endothelial cell lining of the blood vessel(acquired) or the connective tissue supporting the vessels(hereditary) • Symptoms • Superficial bleeding • Hemostatic testing is normal

  6. Vascular Disorders • Inherited • Rare • Bleeding is a common symptom • Conditions • Marfan syndrome • Ehlers-Danlos syndrome

  7. Vascular Disorders: Acquired • Patient exhibits bruising and petechiae • In all acquired disorders, the patient exhibits purpura. • Defects in vasculature is caused by: • Conditions that decrease the supportive connective tissue in the blood vessel walls • Presence of abnormal proteins in the vascular tissues • Infections or allergic conditions • Mechanical stress

  8. Vascular Disorders: acquired • Classification • Purpura due to decreased connective tissue • Collagen and elastin fibers, which form the support for blood vessels, are lost, causing fragility • Senile purpura( elderly people) • Scurvy ( deficiency of vitamin C) • Purpura associated with paraprotein disorders • Purpura due to vasculitis • Inflammation of small blood vessels due to complement activation on subendothelium • drugs and infectious agents

  9. Platelet disorders • Platelet disorders are the most common cause of abnormal bleeding. • Qualitative: abnormalities of platelet function • Quantitative: platelet count is below or above reference range • Hallmarks • Petechiae • Excess bleeding from superficial sites • Mucous membranes, skin

  10. Platelet Abnormalities Agranular platelet Giant platelet

  11. Quantitative Disorders- Its All About the Numbers.. • Thrombocytopenia • Decrease in the number of circulating platelets- below 100,000/µL • Symptom of underlying disease • Bleeding time is prolonged

  12. Quantitative Disorders: Thrombocytopenia • Increased destruction : bone marrow function is normal • Immune Mediated Destruction • Immune Thrombocytopenic Purpura (ITP): • Caused by antibodies that cover the platelets • Acute and chronic forms • Resulting from an unknown cause (Idiopathic) • Often follows a viral infection • Believed to be antibody mediated, may produce a specific platelet autoantibody, specifically IgG. • Spontaneous remission occurs in approximately 80% of the cases • Alloimmune Thrombocytopenia • Alloantibodies stimulated by foreign antigens cause destruction

  13. Acute vs. Chronic ITP

  14. Quantitative Disorders: Thrombocytopenia (Con’t) • Drugs • HIT: Heparin Induced Thrombocytopenia • Heparin causes platelets to activate which eventually causes antibodies to target the heparin/PF4 complex • Results in thrombocytopenia • Other Diseases • Collagen disorders • LE, RA • Infections • Infectious Mononucleosis • HIV

  15. Quantitative Disorders: Thrombocytopenia • Nonimmune: excessive consumption • Platelets are activated without the cascade activating • TTP: Thrombotic Thrombocytopenic Purpura • DIC: Disseminated intravascular coagulation • HUS: Hemolytic uremic syndrome • Mechanical destruction by artificial heart valves

  16. Quantitative Disorders: Thrombocytopenia • Decreased production : bone marrow is abnormal • bone marrow impairment, radiation, malignancy, drugs, congenital conditions • Abnormal distribution • sequestering by the spleen or liver • Excessive dilution • transfusions of stored blood or plasma expanders • Conditions with multiple mechanisms of thrombocytopenia Example: Alcoholism: Patients that have cirrhosis present, can have problems with the coagulation proteins as well as their platelets. Alcohol reduces platelet numbers and causes defects of aggregation, release and procoagulant activity. Platelet production is suppressed by the toxic effect of alcohol on the bone marrow.

  17. Quantitative Disorders • Thrombocytosis • Temporary rise in the number of circulating platelets, secondary to stimulus. Platelets have normal function. • Counts > 1000 x 103/mL • Primary thrombocytosis: uncontrolled production of megakaryocytes • CML • Polycythemiavera • Essential thrombocythemia • Secondary or reactive thrombocytosis: due to another disease or condition • Surgery, particularly splenectomy ( since spleen normally contains 20-30% of the platelets • Inflammation • Acute blood loss • Transient thrombocytosis • Childbirth • Exercise

  18. Qualitative Disorders: Functional • Manifestations include: • Petechiae • Easy and spontaneous bleeding from mucous membranes • Prolonged bleeding from trauma • Lab Diagnosis • Platelet count is normal to slightly decreased • Prolonged bleeding time • PT, PTT, Fibrinolysis tests are normal • Platelet aggregation studies variable

  19. Inherited Disorders of Platelet Function • Disorders of adhesion • Defects in platelet-vessel wall interaction • Disorders of aggregation • Defects in platelet-platelet interaction • Disorders of platelet secretion and abnormalities of granules • Disorders of platelet secretion and signal transduction • Disorders of platelet coagulant-protein interaction

  20. Qualitative (Functional) Disorders: Inherited • Disorders of Platelet Adhesion: platelet to vessel wall interaction • Bernard-Soulier syndrome • Deficiency of a membrane glycoprotein (GPIb/IX) • Giant platelets with coarse granulation and vacules may be seen. • Platelet adhesion, aggregation and bleeding time/ PFA-100 are abnormal • No treatment available, only supportive measures • Von Willebrand’s disease • Deficiency of the von Willebrand factor(vWF) OR production of a dysfunctional protein • Abnormal platelet adhesion and bleeding time/PFA-100 as well as abnormal PTT ( due to VIII defect)

  21. Bernard-Soulier syndrome @2007 Rector and Visitors of the University of Virginia Charles E. Hess, M.D and Lindsey Krstic, B.A.

  22. Qualitative (Functional) Disorders: Inherited • Disorders of Platelet Aggregation: platelet to platelet interaction • Glanzmann’s thrombasthenia • Deficiency of thrombasthenin • Lack the GPIIb/IIIa complex, which is where fibrinogen attaches to platelet surface • Abnormal platelet aggregation, clot retraction and bleeding time • Absence of Fibrinogen

  23. Qualitative (Functional) Disorders: Inherited • Disorders of Platelet Secretion, Abnormalities of granules and Signal transduction • Deficiencies of Dense Granules • Storage pool disease • Platelets appear normal on peripheral smear, but there is a decrease or absence of dense granules • Platelet aggregation abnormal • Deficiencies of Alpha Granules • Gray Platelet Syndrome • Agranular platelets • Defective Thromboxane A2 Synthesis • Platelet secretion and aggregation affected • Defects in Signal transduction • Affects platelet to agonist interactions

  24. Qualitative (Functional) Disorders: Inherited • Disorders of Platelet Procoagulant Activity • Scott syndrome • Activated platelets secrete and aggregate normally but fail to bind coagulation factors

  25. Inherited Platelet Disorders

  26. Qualitative Disorders: Acquired • Uremia • Due to toxin or waste products affect on the platelets • Alcohol: mechanism unclear • Hematologic Disorders • Myeloproliferative Disorders, Acute leukemias, myelodysplasia, multiple myeloma and macroglobulinemia • Drugs • Aspirin: prevents the release of thromboxane A2, thus decreasing platelet secretion. Those platelets affected by aspirin still circulate but are nonfunctional • Antibiotics: penicillins & cephalosporins. Drug coats the platelet membrane blocking ADP and epinephrine receptors, so platelet can not respond to agonist.

  27. Screening Tests of Primary hemostasis

  28. Vascular Damage

  29. References • @2007 Rector and Visitors of the University of Virginia Charles E. Hess, M.D and Lindsey Krstic, B.A • Castellone, D. D. (2010, October). Complexities of Immune Platelet Disorders. Advance for Administrators of the Laboratory, 19(10), 27-30. • http://image.bloodline.net/stories/storyReader$618

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