Bleeding Disorders Vascular and Platelet Disorders

1. Bleeding DisordersVascular and Platelet Disorders Ahmad Shihada Silmi Msc,FIBMS IUG Medical Technology Dept

2. Bleeding Disorder Terms Petechiae-pinpoint size/pinhead size hemorrhagic spots in skin Purpura-hemorrhage under the skin, varying in color and duration Ecchymosis-purplish patch caused by extravasation of blood into skin, larger than petechiae Epistaxis-nosebleed Menorrhagia-excessive menses Hematuria-blood in urine Hemarthrosis-bleeding into joint Hematemesis-vomiting blood Hemoptysis-spitting blood Melena-blood in stool (occult blood)

5. Vessel Defects Causing Bleeding Begins with bleeding episode in presence of normal lab tests for coagulation function Types divided into hereditary and acquired Symptoms are usually of the superficial ones. Usually these diseases are diagnosed by exclusion. After ruling out PLT disorders, coagulation or fibrinolytic disorders in a patient who has bleeding symptoms.

7. Vascular Diseases • PLT count and screening tests for coagulation factors are usually normal. • PLT function tests such as bleeding time and other PLT function tests are also normal, but BT may be prolonged in some vascular diseases.

8. Inherited vascular disorders • They are very rare, and while bleeding is a common symptom, hemostasis tests are NOT necessary for diagnosis.

9. Hereditary Connective Tissue Defects • Defect affects ability to support vessel walls • Examples • Ehlers-Danlos Syndrome • Lack of structural tissue support (collagen disorders) • Skin elasticity and fragility. • Hypermobility of joints • Evidenced by bleeding/bruising • Recurrent joint problems & scarring of the face. • The most serious is deficient of type III collagen (blood vessel type). Which leads to Acute & sever Internal bleeding & sudden death.

10. Hereditary Connective Tissue Defects • Pseudoxanthoma Elasticum • Autosomal recessive trait • Lack of skin elasticity • Some connective tissue calcified • Bleeding and bruising evident

11. Hereditary Vessel Disease • Hereditary Haemorrhagic telangiectasia (HHT) • Inherited as autosomal dominant trait • Defect of angiogenesis • Involves bleeding from abnormally dilated vessels “telangiectasias” • Vessels involved do not contract normally and collapse easily • Patient has pinpoint lesions (tiny areas of bleeding) • Lesions occur on face, hands and feet • May develop at all ages • Blood loss may cause anemia • Diagnosis based on physical appearance

12. Hereditary Vessel Disease • Kasabach-Merritt syndrome (Hemangioma) • Benign tumour of vascular tissue • Grow rapidly to giant proportion. • Threaten the function of neighbouring tissues. • Mechanical injury may result in sever bleeding. • May trigger a localized DIC with thrombocytopeia & consumption coagulopathy, thereby worsening bleeding. • Tumor composed of many blood vessels (blood-filled)

13. Hereditary Vessel Disease • HHT or also called Cavernous Hemangioma • Lesion may swell and bleed • Tumor site may form clots, hemolyzed RBCs and vessel obstruction • Present at birth • Treatment is by surgical removal, if possible,or localized radiotherapy with injection of fibrinolytic inhibitors.

14. Acquired Vascular Disorders • Are seen quite often. • Are characterized by bruising and petechiae

15. Acquired Connective Tissue Defects • Vitamin C Deficiency (Scurvy) • Caused deficient Vitamin C • Vitamin C required for vessel collagen integrity • Acts as “cement” holding endothelial cells together • Lack of Vitamin C prevents proper collagen formation • Result: bleed and vessel fragility • Symptoms include gum bleeding, petechiae and bleeding into tissues and muscles • Treated with Vitamin C

16. Acquired Connective Tissue Defects • Senile Purpura • Occurs in elderly population • Usually benign • Collagen degradation/loss affects vessel integrity • Bruising on arms/hands • No treatment/therapy available

17. Purpura due to Paraproteins • Due to abnormal proteins in the vascular system • Paraproteins are monoclonal Ig produced by a single clone of plasma cells. • Also called M component. • These paraproteins occur in MM, WM, and lymphoproliferative disorders.

18. Cont’d Purpura due to Paraproteins • Symptoms: purpura, bleeding and thrombosis. • The defect is related to multifactors: • Qualitative PLT defects. • Acquired inhibitors. • Deficiency in coagulation factors. • Paraproteins binds Ca, Ca either will not be available for coagulation or the Ca bounded paraproteins will interfere with coagulation. • Thrombocytopenia.

19. Cont’d Purpura due to Paraproteins • Bleeding symptoms include: • Epistaxis • Petechiae, • Purpura, and • Retinal bleeding.

20. Purpura due to Paraproteins • Amyloidosis • Occur as primary disease or is associated with paraproteinemias. • Deposition of amyloid on skin and vascular walls. • Leads to fragility of vessel walls.

21. Other Vascular Disorders • Self-produced “autoantibodies” damage to vessels • Caused by drugs resulting in purpura • Caused by allergic/immune disturbance • Evidenced by swelling, ulcers, purpura and lesions and other symptoms • Affects children • Other allergic purpura-Hemoch-Schonlein variety • Accompanied by joint and abdominal pain • Avoidance of allergen aids recovery

22. Other Vascular Disorders • Infectious purpura • Observe petechiae and purpura • Results from • Inflammatory response to agent • Autoimmune/autoantibody response • Bacterial products or toxins • Injury caused by agent • Low platelets observed and DIC • Cure is to treat infection

24. Platelet Disorders Classification: Quantitative PLT Disorders Thrombocytopenia Thrombocytosis PLT Reference Range = 150 - 450 x109/L Thrombocytopathy Qualitative PLT Disorders

25. Thrombocytosis • Thrombocytosis resulting from myeloproliferation • essential thrombocythemia • polycythemia vera • chronic myelogenous leukemia • myeloid metaplasia • Secondary (reactive) thrombocytosis • systemic inflammation • malignancy • iron deficiency • hemorrhage • postsplenectomy

26. Thrombocytopenia • Reduced platelet count. • The most common cause of excess or abnormal bleeding. • As anemia is a symptom of a disease as we have seen in Hematology #1, thrombocytopenia is also a symptom of a disease!

27. Do not forget to assure that the case you have is a real thrombocytopenia and not Pseudothrombocytopenia Platelet clumping, or aggregation Platelet Satelltism Pseudothrombocytopenia

28. Thrombocytopenia

29. Hemostatic Level • Hemostatic Platelet count level is more than 50 x109/L. • This means that normal hemostasis may occur ≥ 50 x109/L

30. Classification: platelet disorders

31. Thrombocytopenia

32. General characteristics of platelet disorders • characterized by variable mucocutaneous bleeding manifestations. • excessive hemorrhage may follow surgical procedures or trauma. • Platelet counts and morphology are normal. • prolonged bleeding time, • Abnormal Platelet aggregation and secretion studies

33. Thrombocytopenia • Usually mucosal bleeding • Epistaxis, menorrhagia, and GI bleeding is common • Trauma does not usually cause bleeding

34. Thrombocytopenia • Three mechanisms of Thrombocytopenia • Decreased production • Usually chemotherapy, myelophthisic disease, or BM effects of alcohol or thiazides • Splenic Sequesteration • Rare • Results from malignancy, portal hypertension, or increased Splenic RBC destruction ( hereditary spherocytosis, autoimmune hemolytic anemia) • Increased Destruction

35. Thrombocytopenia • Immune thrombocytopenia • Multiple causes including drugs, lymphoma, leukemia, collagen vascular disease • Drugs Include • Digitoxin, sulfonamindes, phenytoin, heparin, ASA, cocaine, Quinine, quinidine, glycoprotein IIb-IIa antagonists • After stopping drugs platelet counts usually improve over 3 to 7 days • Prednisone (1mg/kg) with rapid taper can shorten course

36. Thrombocytopenia • HIT • Important Immunologic Thrombocytopenia • Usually within 5-7 days of Initiation of Heparin Therapy but late onset cases are 14-40 days • Occurrence 1-5% with unfractionated heparin and less than 1% with low molecular-weight heparin • Thrombotic complications in up to 50% of HIT with loss of limb in 20% and mortality up to 30%

37. ITP • Diagnosis of exclusion • Associated with IgG anti-platelet antibody • Platelet count falls to less that 20,000

39. ITP • Acute Form • Most common in children 2 to 6 years • Viral Prodrome common in the 3 weeks prior • Self Limited and > 90% remission rate • Supportive Treatment • Steroids are not helpful

40. ITP • Chronic Form • Adult disease primarily • Women more often than men • Insidious onset with no prodrome • Symptoms include: easy bruising, prolonged menses, mucosal bleeding • Bleeding complications are unpredictable • Mortality is 1% • Spontaneous remission is rare

41. ITP • Chronic Form • Hospitalization common because of a complex differential diagnosis • Multiple treatments • Platelet transfusions are used only for life threatening bleeding • Life threatening bleeding is treated with IV Immune globulin (1g/kg)

42. TTPHUS • Exist on a continuum and are likely the same disease • Diagnosed by a common pentad • Microangiopathic Hemolytic Anemia: Schistocytes membranes are sheared passing through microthrombi • Thrombocytopenia: More sever in TTP • Fever • Renal Abnormalities: More prominent in HUS: include Renal insufficiency, azotemia, proteinuria, hematuria, and renal failure • Neurologic Abnormalities: hallmark of TTP 1/3 of HUS: Sx of HA, confusion, CN palsies, seizure,coma

43. TTPHUS • Labs • PT, PTT, and fibrinogen are within reference range • Helmet Cells (Shistocytes) are common

44. TTPHUS • HUS • Most common in infants and children 6mo - 4 years • Often associated with a prodromal diarrhea • Strongest association to E. coli O157:H7 but also associated with SSYC as well as multiple virus • Prognosis • Mortality 5-15% • Younger patients do better

45. TTPHUS • HUS • Treatment • Mostly supportive • Plasma exchange reserved for sever cases • Treat hyperkalemia • Avoid antibiotics with Ecoli • May actually increase verotoxin production. • May be helpful with cases of Shigella dysenteriae

46. TTPHUS • TTP • More common in adults • Untreated mortality rate of 80% 1 to 3 months after diagnosis • Aggressive plasma exchange has dropped the mortality to 17% • Splenectomy, immune globulin, vincristine all play a role in therapy

47. TTPHUS • AVOID PLATELET TRANSFUSION • May lead to additional microthrombi in circulation • Transfuse only with life threatening bleeding

48. Dilutional Thrombocytopenia • PRBC are platelet poor • Monitor platelet count with every 10 u PRBC • (for each 8-10 units of PRBC, 2 units of FFP & 5 units of platelet concentrate are given) • Transfuse when count below 50,000 • Get them upstairs before you transfuse 10 units PRBC

49. Bleeding Clinical Correlation - PLT Numbers BT prolongation proportional to PLT count IF no complicating factors.

50. Significant Lab Data in Defects of Primary Hemostasis