1. Bleeding disorders Doc. MUDr. L. Boudová, Ph.D.

2. Bleeding disorders I. Vessels - increased fragility II. Platelets - deficiency or dysfunction III.Coagulation disorders IV.Combination I-III I. Vessels infections, drugs (hypersensitivity) poor vascular wall: Ehlers-Danlos, scurvy; Cushing syndrome, old people hereditary hemorrhagic teleangiectasia amyloid

3. Thrombocytes 150-300 000/mm 3 normal 100 000/mm 3 thrombocytopenia 50 000/mm 3 posttraumatic bleeding 20 000/mm 3 spontaneous bleeding

4. Thrombocytopenia decreased production increased destruction sequestration dilution

5. Splenomegaly a sign of an underlying disease a problem per se bigger spleen~ bigger function = destruction of blood cells Hypersplenism 1.splenomegaly 2.(pan) cytopenia 3.correction of blood cytopenia by splenectomy

6. Immune thrombocytopenic purpura Idiopathic TP – but autoimmune! Antibodies against platelets Primary or secondary

7. ITP Acute – children Abrupt onset, both sexes, 2 weeks after virosis, resolves within 6 mo, 20% chronic Chronic – adults (F:M 3:1) Petechial hemorrhages and ecchymoses Easy bruising, skin, mucosa, nose, gums, soft tis., melena, hematuria, menstruation Clin.: nonspecific – reflective of thrombocytopenia

8. ITP - organs Spleen - normal size PB: megathrombocytes BM:+ /- more megs Therapy: splenectomy

9. Thrombotic microangiopathies related clinical syndromes thrombotic thrombocytopenic purpura (TTP) hemolytic-uremic syndrome (HUS) ENDOTHELIAL INJURY WIDESPREAD HYALINE MICROTHROMBI OVERLAP - common features (TTP, HUS): thrombocytopenia microangiopathic hemolytic anemia fever

10. Thrombotic microangiopathies thrombotic thrombocytopenic purpura (TTP) hemolytic-uremic syndrome (HUS) Versus Disseminated intravascular coagulation Common: hyaline thrombi !!Differences: DIC: primary importance: activation of clotting system

11. Thrombotic microangiopathies related clinical syndromes thrombotic thrombocytopenic purpura (TTP) hemolytic-uremic syndrome (HUS) ENDOTHELIAL INJURY WIDESPREAD HYALINE MICROTHROMBI OVERLAP - common features (TTP, HUS): thrombocytopenia microangiopathic hemolytic anemia fever

12. Thrombotic microangiopathies TTP neurological deficits (transient) renal failure adult women HUS mostly no neurol. sympt. acute renal failure DOMINANT! children; E. coli O157:H7, verotoxin Common: thrombocytopenia, microangiopathic hemolytic anemia, fever

13. Microangiopathic hemolytic anemia hemolytic-uremic syndrome several fragmented red cells

14. Thrombotic microangiopathies thrombotic thrombocytopenic purpura (TTP) hemolytic-uremic syndrome (HUS) Versus Disseminated intravascular coagulation Common: hyaline thrombi !!Differences: DIC: primary importance: activation of clotting system

15.  secondary complication of some serious condition  consumption coagulopathy  thrombohemorrhagic diathesis  acute, subacute, chronic Disseminated intravascular coagulation (DIC)

16. DIC: t hrombotic and hemorrhagic diathesis Microthrombi hypoxia, infarctions Consumption →depletion of platelets and clotting factors + secondary activation of fibrinolysis hemorrhages activation of coagulation sequence

17. Mechanisms of DIC trigger 1. Release of tissue factor or thromboplastic substances 2. Widespread endothelial injury

18. DIC 1. obstetrics – 50%; abruptio placentae, retained dead fetus, septic abortion, amniotic fluid embolism, toxemia 2. neoplasms – 30%; adenocarcinomas, AML 3. infections – gram-negative sepsis 4. trauma, burns, extensive surgery 5. Other – snakebite, heat stroke, giant hemangioma, aortic aneurysm etc.

19. DIC Morphology microthrombi Kidneys hemorrhages Microinfarcts, bilat. renal necrosis lungs Brain - microinfarcts, hemorrhage Placenta Spleen, liver Endocrine organs: pituitary, adrenals

20. DIC - clinical microangiopathic hemolytic anemia, RDS – dyspnea, cyanosis neurologic symptoms, oliguria, acute renal and circulatory failure, Convulsions, coma SHOCK

21. Disseminated intravascular coagulation hyaline thrombi

22. Sy Waterhouse - Friedrichsen