Haemorrhagic Disorders
Dr. Bashar Department of Pathology Mosul Medical CollegeHaemorrhagic Disorders
These include Disorders of platelets. Disorders of blood vessels. Disorders of coagulation & fibrinolysis.Platelet Disorders
Quantitative : Thrombocytopenia. Qualitative : Platelet defects (dysfunction)Thrombocytopenia
Thrombocytopenia exists when platelet count is less than 150 x 109 /L .Normal platelet count = 150 – 400 x 109 /LBleeding is unusual when count is >50x109 /L Spontaneous bleeding occurs when count is < 20x109 /LCauses of Thrombocytopenia
1.decresed platelet productiona. Aplastic anaemia. b. Megaloblastic anaemia ( decrease Vit. B12 or /and decrease folic acid ). c. Bone marrow infiltration by neoplasms. d. Cytotoxic drugs ( Dose Dependant ). e. Ionizing radiation (Dose Dependant ). f. Drugs; cause thrombocytopenia in some recipients : Metheprim, Phenylbutazone, Gold compounds . g. Alcohol.
2. Increased destruction of platelets
Causes of Increased Destruction of Plateletshypersensitivity to drugs . Drugs : Chlorothiazides , Digoxin , Methyl- dopa ,PAS ( para-aminosalicylic acid ), Quinine, Quinidine, Sulphonamides .
Autoimmune Thrombocytopenia Autoantibodies usually of IgG class either asisolated disorder :idiopathic (immune ) thrombocytopenic purpura ( ITP)in association with other autoimmune disorders : SLE ,myasthenia gravis ,Evan’s syndrome( autoimmune hemolytic anemia + autoimmune thrombocytopenia), lymphoma , chronic lymphocytic leukaemia
ITP (Idiopathic {Immune} Thromocytopenic Purpura)
Occurs chiefly in children and young adultsCharacter
Children
Adults
Behavior (onset)
Acute (sudden)
Chronic (insidious)
Peak age incidence
2-8 years
20-40 years
Sex
F=M
3F:1M
Duration
<6 months (usually weeks )
> 6 months (often years )
Associated disorders
Preceding viral infection
None
Responsible antibody usually belongs to subclass 3 of IgG. Clinically Varies from mild cutaneous bleeding to gross uterine or GIT hemorrhage . In severe cases it lead to intracerebral hemorrhage . Treatment Steroids Immunosuppressive drugs Splenectomy
Blood: Hb – Normal WBC – Normal Platelet count reducedIn severe cases 20 – 50 x 109/L. In moderate cases ( 50 – 80) x 109/L. Bleeding: Skin:Epistaxis GIT, GUT bleedings. CNS “ fatal” very rare. Ecchymosis (Bruises)
Petechie
3. Hypersplenism Clinical syndrome : Enlargement o f the spleen. Reduction in one or more of cell lines of blood (anemia, leucopenia, thrombocytopenia). Normal bone marrow. Cure after splenectomy.
4.DIC(disseminated intravascular coagulation) This causes thrombocytopenia by excessive utilization & destruction of platelets . 5. Massive blood transfusion
Qualitative Platelet Defects
Platelet count is normal ,but there is defect in platelet aggregation . e.g. Glanzmann’s disease (thrombosthenia, autosomal recessive )Disorders of Blood Vessels ( Vascular Purpra )
Congenital : Hereditary Hemorrhagic Telagiectasia Autosomal dominant Clinically: usually epistaxis , multiple telangiectatic spots in the skin & mucus membranes leading to hemorrhage & iron deficiency anemia ,haemoptysis.Acquired : Purpura simplex in women . Senile purpura :on the dorsum of hands & arms due to poor capillary support from collagen as also in : Steroid therapy or Cushing syndrome Scurvy ,vit. C needed for polymerization of mucopolysaccharides necessary for collagen synthesis .
Henoch Schonlein Purpura : necrotizing vasculitis give rise to small hemorrhages especially in the skin & gut ,there may be associated glomerulonephritis ,usually follow streptococcal infection. Damage to capillaries as in : severe acute bacterial infection: septicaemia. subacute bacterial endocarditis .
Disorders of Coagulation
contact XII XIIa Tissue factor(III)+VII e.g.collagen fibres XI XIa X VIII,Ca++ Phospholipid IX IXa Xa V Phospholipid Ca++ Prothrombin(II) Thrombin (IIa) Fibrinogen Fibrin XIII (Fibrin Stabilizing Factor)Inherited Disorders of Coagulation
Of these coagulation factors deficiencies factor VIII deficiency is important .it can lead to Haemophilia A and von Willebrand’s disease .Haemophilia A
Hereditary abnormality of coagulation.Sex linked : affect ♂ ,while ♀ are carriers .Xْ Y XX YX YX Xْ X Xْ X Normal ♂ Carrier ♀ All sons of diseased ♂ are normal . All daughters of diseased ♂ are carriers .
50% of daughters of carrier female are carriers .50% of sons of carrier female are diseased . XY Xْ X XXْ XX YXْ YX
Clinically
Male child will suffer from bleeding following circumcision , haemarthrosis usually after crawling . Severity of haemophilia is graded according to the level of VIII C into: Severe ( VIII C < 1% of normal ). Moderate ( 2-3% of normal). Mild ( 5-20% of normal).Diagnosis
APTT ↑Clotting time either normal or ↑Bleeding time normal VIII C activity ↓VIII C : Ag ↓VIII R: Ag normal
Factor IX deficiency ( Haemophilia B or Christmas Disease )
Inherited disorder shows the same pattern of inheritance as haemophilia A (sex linked ). Same clinical picture but incidence of disease = 1/5th of the haemophilia A . Treated by factor IX concentrate .Acquired Disorders Of Coagulation
Vitamin K deficiency Vitamin K is necessary for γ carboxylation of precursors of factor II ( prothrombin ) & some other coagulation factors. It is fat soluble ,present in leaf vegetables & also synthesized by the normal intestinal flora.Dietary deficiency of sufficient severity to produce bleeding is well recognized in:
Neonates (Haemorrhagic Diseases of the newborn) in whom normal bacterial flora is not yet established. In children & adults( malnourishment). ↓ absorption in billiary obstruction, coeliac disease.Liver disease Liver is the site of synthesis of most coagulation factors. Severe impairment of liver lead to combined factor deficiency particularly II , VII ,IX ,X, & I (fibrinogen).
Renal Impairment Lead to thrombocytopenia ,platelet dysfunction ,(II ,VII ,IX ,X ,XIII ) ,DIC.
Warfarin therapy Oral anticoagulant act as competitive inhibitor of vit. K ,suppressing the synthesis of four vit. K dependant clotting in the liver prothrombin ( factor ll ,VII ,IX & X .
Doing prothrombin time Control = seconds. Test = seconds. Test/control ratio (R) = INR (international normalized ratio ) = Accepted INR = 2 - 3.5 INR = (R)^s S= sensitivity index ,fixed figure provided by manufacturer of the kit ( e.g S = 2)
Control of Warfarin Therapy by