7b..bleeding disorder

BLEEDING BLEEDING DISORDERSDISORDERS

DR.RAFI AHMED GHORI

Professor

Medical Unit I

LUMHS Jamshoro.

BLEEDING DISORDERBLEEDING DISORDER

Definition:Definition:Disorder characterized bySpontaneous bleeding.Excessive bleeding

following trauma.

EtiologyEtiology

VESSEL WALL ABNORMALITIES:

PLATELETS DISORDER:

COAGULATION DISORDER:

VESSEL WALL ABNORMALITIES:VESSEL WALL ABNORMALITIES:Vessel wall abnormalities may be congenital OR acquired i-e

vasculitis may result in purpuric lesions.

CAUSES OF NON-THROMBOCYTOPENIC PURPURA: 1.   Senile purpura 2.   Fictitious purpura 3.   Henoch-Schonlein purpura 4.   Vasculitis 5.   Paraprotienaemias 6.   Purpura fulminans 7.   Embolic purpura 

VESSEL WALL ABNORMALITIES:VESSEL WALL ABNORMALITIES:HERIDITARY HEMORRHAGICTELANGECTSIASIS: Dominant inherited condition. There is a telengectiasis and

small aneurysms found on finger tips, face, nasal passages, tongue and GIT.

Small group of people develop pulmonary A/V malformation. Pt either develops recurrent bleeding/epistaxis/iron deff:

anemia due to occult GIT bleeding.

Rx.Rx. Iron therapy for blood loss. .Local cautery/laser therapy for single lesion from bleeding

(epistaxis). Estrogens may be tried. 

VESSEL WALL ABNORMALITIES:VESSEL WALL ABNORMALITIES:

EHLERS DANLOS DISEASE:Congenital disorder of collagen

synthesis in which capillaries are poorly supported by s/c collagen and ecchymosis are commonly observed.

PLATELETS DISORDER:PLATELETS DISORDER:  QUANTITATIVE PLATELETS

DYSFUNCTION

QUALITATIVE PLETELET DISORDER:

PLATELETS DISORDER:PLATELETS DISORDER:QUANTITATIVE PLATELETS QUANTITATIVE PLATELETS DYSFUNCTION DYSFUNCTION ((Thrombocytopenia) Thrombocytopenia) Mechanism: 1 Failure of megakaryocytic maturation. 2 Excessive platelets consumption after their release into

circulation i-e ITP, DIC etc. 3 Platelets sequestration in enlarged spleen i-e

HYPERSPLEENISM. S/S:     Petechial cutaneous bleeding, intracranial bleeding and

oozing from mucus membrane/surface.      Characterized by decreased platelets count and prolong

bleeding time.

((Thrombocytopenia) Thrombocytopenia) Causes:Causes:Marrow Disorder Aplastic anemia Hematologic

malignancy Myelodysplastic

disorder B12 deff. Chronic alcoholism

Non Marrow DisorderImmune disordersITPDrug inducedSec: CLL, SLEPost transfusionDICTTPHU syndrome HyperspleenismSepsisHeamangiomasViral infectionLiver failure.

Management:

• Rx Underlying cause

• Platelet transfusion

IDIOPATHIC THROMBOCYTOPENIC IDIOPATHIC THROMBOCYTOPENIC PURPURA.PURPURA.

Autoimmune antibody IgG is formed against unknown antigen of platelets membrane/surface.

Antipletelet antibody binds to complement, platelets are not destroyed by direct lysis.

Rather destruction takes place in spleen, where spleenic macrophages with Fc bind to antibody coated platelets.

IDIOPATHIC THROMBOCYTOPENIC IDIOPATHIC THROMBOCYTOPENIC PURPURA.PURPURA. (Clinical Features) (Clinical Features)

In Children:Often precipitated by viral infection and usually

self limited Asymptomatic not febrile. Present with mucosal/skin bleeding,

mennorrhagia, purpura, petechiae.Adults:       Commonly affects female.       Ratio 2:1 (male/female ratio)       Peak incidence 20-50 years of age.

IDIOPATHIC THROMBOCYTOPENIC IDIOPATHIC THROMBOCYTOPENIC PURPURA.PURPURA. Δ LAB: platelets below 10,000 /ml. Bone marrow will appear normal.Rx PREDENISONONE: 1-2 mg/kg/day. SPLEENECTOMY: immunoglobulin 1g/kg/day 2-3 days. DANAZOLE: 600mg/day response rate is 50% IMMUNOSUPPERESSIVE DRUGS: i-e vincristine,

vinblastine, azathioprine, cyclosprin, cyclophosphomide.Prognosis: The prognosis for remission is good. Disease is initially

controlled with prednisolone, spleenectomy is definite Rx.

EVANS SYNDROME:EVANS SYNDROME:

ITP + Autoimmune hemolytic anemia 10% cases.

These pts shows spherocytosis, reticulocytosis + anemia.

THROMBOTIC THROMBOCYTOPENIC THROMBOTIC THROMBOCYTOPENIC PURPURA:TTP: PURPURA:TTP:

TIP is an uncommon syndrome with Microangiopathic hemolytic anemia, Thrombocytopenia and Markedly increased LDH, Non-infectious fever, Neurologic disorder, Renal abnormalities are less commonly seen.Pathogenesis may be diff: of von Willibrand’s disease

factors clearing protease, in some case antibody directed against protease.

TTP:TTP:

Clinical features:20-25 yrSlightly common in female.AnemiaBleedingFever Neurological symptomsHead acheConfusion aphasiaAltered consciousness Hemi paresis + seizures.

TTP:TTP:

LAB:Blood CP

Anemia

Reticulocytosis

Circulating nucleated cells. Microangiopathic picture

Fragmented RBC’s i-e (schistocytes, helmet cells, triangle forms)

Thrombocytopenia.

Hemolysis, Increased Indirect bilirubinHemoglobinemia Methem-albuminia.Increased LDH.Coomb’s test –ve.Coagulation test: Normal PT, APPTT, fibrinogen.Elevated. FDP(fibrin degradation product) may be

TTP:TTP:Rx:Plasmapheresis with /without prednisone, anti

platelets aspirin 325 mg/daily , dipyridamole 75 mg × TDS may be given.

Combination spleenectomy, steroids and dextran may be used with success.

Immuno suppressive therapy i-e (cyclophosphomide).

Prognosis:80-90 % Pts recover completely with plasma

pharesis while 20% pts will be chronic and relapsing.

QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER

CONGENITAL:

Glansmann’s thrombosthenia

Bernard souliar syndrome

Storage pool disease

•ACQUIRED

•Myeloproliferative disorder.

•Uremia

•Drugs i-e NSAIDS Aspirin

•Autoantibody

•Paraprotiens

•Acquired storage pool disease

•Fibrin degradation products

•Von Willibrand’s disease

QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER

BERNARD SOULIER SYNDROME:BERNARD SOULIER SYNDROME: Autosomal recessive intrinsic platelets disorder. lack of glycoprotein (41 b) receptor for von Willibrand’s

factor.Clinical Features: Presents with mucosal bleeding and post operatively as

well.LAB: Thrombocytopenia may be present, and abnormally large. BT is prolonged Von Willibrand’s factor Normal Rx: Platelet transfusion

QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER

GLANSMANN’s THROMBASTHENIA:GLANSMANN’s THROMBASTHENIA: Autosomal recessive disorder. Lack of receptors (containing glycoprotein II b + III a) for

fibrinogen on platelets.Clinical Features: Mucosal bleedingLAB: Platelets no’s and morphology are normal B.T is prolonged Platelets fails to aggregate in respond to typical agent (ADP,

collagen, thrombin) but aggregate in respond to risocetin.Rx: Platelet transfusion

QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER

VON-WILLIBRAND’S DISEASE:VON-WILLIBRAND’S DISEASE:

Autosomal dominant and gene for (VWF) is located on chromosome 12.

VWF is synthesized by endothelial cells and megakaryocytic

It acts as carrier protein for factor VIII which it is non-covalently bound. A defect therefore leads to decreased plasma factor VIII level.

It forms bridges b/w platelets and sub endothelium eg collagen allowing platelets to adhere to damaged vessel walls. There fore defect of VWF leads to prolong bleeding after minor trauma.

QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDER

VON-WILLIBRAND’S DISEASE:VON-WILLIBRAND’S DISEASE:

Clinical Features: Mucosal bleeding as already discussed.LAB: Reduced level of VWF which often accomplished by sec:

reduction in factor VIII and prolonged bleeding time (B.T)

Rx: MILD HAEMORRHAGES:Desmopressin 0.3 μg/kg, after which VWF levels usually

raise 3 in 30-90 minutes MASSIVE HAEMORRHAGES:Factor VIII

COAGULATION DISORDER:COAGULATION DISORDER:

Coagulation factor disorder can either can either arise from single factor usually “congenital deficiency” eg factor VIII resulting in HAEMOPHILIA-A or multiple factor which is acquired eg Sec: to liver disease or warfarin therapy.

HEAMOPHILIA – A (CLASSIC TRUE HAEMOPHILIA)

HAEMOPHILLIA – B (CHRISTMAS DISEASE)

COAGULATION DISORDER:COAGULATION DISORDER:CONGENITAL BLEEDING CONGENITAL BLEEDING DISORDER:DISORDER:

HEAMOPHILIA – A (CLASSIC TRUE HEAMOPHILIA – A (CLASSIC TRUE HAEMOPHILIA)HAEMOPHILIA) X-linked disorder Due to defect of factor VIIIC/F: Bleeding occurs as bruising when babies are about 6 month

old.Trauma results in excessively bleeding. Recurrent bleeding hemorrhage at following sites knee, elbow, ankle, and hip. Mucus membrane internal bleeding of mouth, lips, gums,

brain and kidney Muscle haematoma esp. calf and Psoas muscle Rx Factor VIII infusion

HAEMOPHILLIA – B (CHRISTMAS HAEMOPHILLIA – B (CHRISTMAS DISEASE)DISEASE)

Due to deff: of factor IX S/S: Same in type ARx Factor IX infusionLONG TERM COMPLICATIONCOMPLICATION due to repeated hemorrhage: Arthropathy of large joints eg knee, elbow Muscle atrophy due to haematoma Mononeuropathy due to pressure of haematoma.COMPLICATION due to therapy Antifactor VIII antibody develops Virus transmission Hepatitis A-B-C-D + HIV

COAGULATION DISORDERCOAGULATION DISORDERACQUIRED BLEEDING ACQUIRED BLEEDING DISORDERDISORDER

DICLIVER DISEASE RENAL DISEASE

DISSAMINATED INTRAVASCULAR DISSAMINATED INTRAVASCULAR COAGULATIONCOAGULATION

DIC is condition characterized by thrombosis within circulation. DIC can be induced by variety of different mechanism.

Endothelial cell damage eg endotoxic in G –ve septicemia results in tissue factor release which in turn leads to coagulation cascade through extrinsic pathway.

The presence thromboplastin from damaged tissue, placenta, fat embolus/following brain injury may activate coagulation

This results in consumption of platelets and coagulation factors which secondarily activation of fibrinolysis leading to bleeding tendency.

DICDIC::CAUSESInfectious: E Coli Nessieria meningitis Strep pneumonia Malaria

Obstetric RPOC Abruptio placentae Amniotic fat embolisms Pre-eclampsia

Cancer Lung Pancreas Prostate

CLINICAL FEATURES:

Bleeding, thrombosis, bleeding far from common than thrombosis.

Subacute DIC:

Occurs primarily in cancerous pts results in superficial + deep venous thrombosis.

Other Manifestation:

High incidence of cardio respiratory failure

DICDIC

LAB:ThrombocytopeniaProlong PTAPPTT may be

normal/increasedLow fibrinogenIncreased level D-dimmer

Treatment of DICTreatment of DIC

Rx Underlying cause.General Measures: Correction of dehydration Renal failure Acidosis and ShockReplacement: Platelets transfusion if platelets counts below 10,000μg/l Fibrinogen with cryoprecipitate to maintain plasma

fibrinogen level above 150 mg/dl FFP When thrombosis i-e DVT, Pulmonary their give Heparin.

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