Bleeding

Haemorrhagic Disorders

Dr. Sura Obay aldewachi

at the end of this lecture you will learn

Thrombocytopenia Vascular purpura. Inherited disorders of coagulation.

Hemorrhagic Disorders

Disorders of platelets. Disorders of blood vessels. Disorders of coagulation & fibrinolysis. Platelet DisordersQuantitative : Thrombocytopenia.Qualitative : Platelet defects. 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 /L

Causes of Thrombocytopenia

Decreased platelet production Characterized by reduction of megakaryocytes in bone marrow & by small mean size of circulating platelets (Mean Platelet Volume –MPV ) and association with anemia and leucopenia : a. Aplastic anaemia. b. Megaloblastic anaemia ( decrease Vit. B12 or /and decrease folic acid ). c. Bone marrow infiltration by neoplasms. d. Cytotoxic drugs ( Dose Dependent ). e. Ionizing radiation (Dose Dependent ). f. Drugs; cause thrombocytopenia in some recipients : Metheprim, Phenyl butazone, Gold compounds . g. Alcohol.

Increased destruction of platelets Characterized by normal or increased numbers of megakaryocytes in bone marrow , circulating platelets appear larger than normal ( raised MPV) and that platelets are usually only affected ( no anemia or leucopenia ). Causes of increased destruction of platelets: Hypersensitivity to drugs Occurs suddenly following single dose drugs act as a hapten forming antigenic complex by binding to plasma protein and then antibody ( usually IgG) is formed against this complex , this antigen-antibody complex then binds to platelets leading to destruction by phagocytosis usually in the spleen . Drugs : Chlorothiazides , Digoxin , Methyl- dopa ,PAS ( para-aminosalicylic acid ), Quinine, Quinidine, Sulphonamides.


Autoimmune Thrombocytopenia Autoantibodies usually of IgG class either as Isolated disorder: idiopathic (immune )thrombocytopenic purpura ( ITP). OR in association with other autoimmune disorders: SLE ,myasthenia gravis ,Evan’s syndrome (autoimmune hemolytic anemia + autoimmune thrombocytopenia), lymphoma , chronic lymphocytic leukemia.

ITP (Idiopathic((immune)) Thromocytopenic Purpura)

Occurs chiefly in children and young adults
Character
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:Epistaxis GIT, GUT bleedings. CNS “ fatal” very rare. Ecchymosis (Bruises)
Petechie


III. Hypersplenism Clinical syndrome characterized by : Enlargement of the spleen. Reduction in one or more of cell lines of blood (anemia, leucopenia, thrombocytopenia). Normal bone marrow. Cure after splenectomy. IV. DIC(disseminated intravascular coagulation) This causes thrombocytopenia by excessive utilization & destruction of platelets . V. 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 Telangiectasia Autosomal dominant Clinically: usually epistaxis , multiple telangiectatic spots in the skin & mucus membranes leading to hemorrhage & iron deficiency anemia , hemoptysis.

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: septicemia. 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 .Structure of factor VIIIPlasma factor VIII is now considered to be a complex of two components ;the larger of the two ,factor VIII /von Willebrand factor ( VIII R: WF) is coded by autosomal genes and is deficient in von Willebrand ‘s disease , it promotes primary haemostasis by interacting with platelets and also appears to function as a carrier of smaller component factor VIII coagulant (VIII C) which is coded by an X chromosome which participates directly into cascade clotting reaction & is deficient in classical haemophilia ,when assayed immunologicaly these two components are expressed as antigen (Ag) i.e. VIII R: Ag and VIII C : Ag .


Haemophilia A
Hereditary abnormality of coagulation.Sex linked : affect ♂ ,while ♀ are carriers .

Xْ Y XX YX YX Xْ X XْX 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 , hemarthrosis 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 ↓

Von Willebrand’s Disease Inherited hemorrhagic disease in which bleeding time is prolonged due to deficiency of von Willebrand’s factor (vllll R) as this factor is important for platelet adhesion to vascular subendothelium.Comparison Between Haemophilia & von Willebrand’s Disease

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 CoagulationVitamin 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 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) Heparin therapy control Coagulation ( Clotting ) time Thrombin time Activated Partial Thromboplastin Time (APTT
Control of Warfarin Therapy by

Disseminated Intravascular Coagulation (DIC)

wide spread deposition of fibrin in the small vessels of many organs causing tissue necrosis & multiple organ dysfunction and subsequent bleeding state due to consumption of platelets & clotting factors and secondary enhancement of fibrinolytic activity . Microangiopathic hemolytic anemia is a common accompaniment. Causes Extensive burn Septicemia Shock Liver disease Renal disease Complications of labour : retroplacental haemorrhage & aminotic fluid embolism.

DIC: Disseminated Intravascular Coagulation: 1) Bleeding: “ Consumption coagulopathy” Platelets (severe) Coagulation factors (I, II, VIII, IX, X) Fibrinolysis 2) Haemolytic Anemia “ Microangiopathic” Hb pcv RBC Fragmentation Retic Indirect S. Bilirubin. Hb uria3) Thrombotic manifestations: 1) Acute Renal failure 2) Skin Necrosis. 3) CNS ischemia 4) Respiratory Distress.