VESSEL WALL ABNORMALITIES:VESSEL WALL ABNORMALITIES:Vessel wall abnormalities may be congenital OR acquired i-evasculitis 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 andsmall aneurysms found on finger tips, face, nasal passages,tongue and GIT. Small group of people develop pulmonary A/Vmalformation. 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 collagensynthesis in which capillaries are poorlysupported by s/c collagen andecchymosis are commonly observed.
IDIOPATHIC THROMBOCYTOPENICIDIOPATHIC THROMBOCYTOPENICPURPURA.PURPURA.Autoimmune antibody IgG is formed againstunknown antigen of platelets membrane/surface.Antipletelet antibody binds to complement, plateletsare not destroyed by direct lysis.Rather destruction takes place in spleen, wherespleenic macrophages with Fc bind to antibodycoated platelets.
IDIOPATHIC THROMBOCYTOPENICIDIOPATHIC THROMBOCYTOPENICPURPURA.PURPURA. (Clinical Features)(Clinical Features)In Children:Often precipitated by viral infection and usuallyself 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 THROMBOCYTOPENICIDIOPATHIC THROMBOCYTOPENICPURPURA.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 initiallycontrolled with prednisolone, spleenectomy is definite Rx.
THROMBOTIC THROMBOCYTOPENICTHROMBOTIC THROMBOCYTOPENICPURPURA:TTP:PURPURA:TTP:TIP is an uncommon syndrome withMicroangiopathic hemolytic anemia,Thrombocytopenia andMarkedly increased LDH,Non-infectious fever,Neurologic disorder,Renal abnormalities are less commonly seen.Pathogenesis may be diff: of von Willibrand’s diseasefactors clearing protease, in some case antibodydirected against protease.
TTP:TTP:Clinical features:20-25 yrSlightly common in female.AnemiaBleedingFeverNeurological symptomsHead acheConfusion aphasiaAltered consciousnessHemi paresis + seizures.
TTP:TTP:Rx:Plasmapheresis with /without prednisone, antiplatelets aspirin 325 mg/daily , dipyridamole 75mg × TDS may be given.Combination spleenectomy, steroids and dextranmay be used with success.Immuno suppressive therapy i-e(cyclophosphomide).Prognosis:80-90 % Pts recover completely with plasmapharesis while 20% pts will be chronic andrelapsing.
QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDERCONGENITAL:Glansmann’sthrombostheniaBernard souliarsyndromeStorage 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 DISORDERBERNARD SOULIER SYNDROME:BERNARD SOULIER SYNDROME: Autosomal recessive intrinsic platelets disorder. lack of glycoprotein (41 b) receptor for von Willibrand’sfactor.Clinical Features: Presents with mucosal bleeding and post operatively aswell.LAB: Thrombocytopenia may be present, and abnormally large. BT is prolonged Von Willibrand’s factor NormalRx: Platelet transfusion
QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDERGLANSMANN’s THROMBASTHENIA:GLANSMANN’s THROMBASTHENIA: Autosomal recessive disorder. Lack of receptors (containing glycoprotein II b + III a) forfibrinogen 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 DISORDERVON-WILLIBRAND’S DISEASE:VON-WILLIBRAND’S DISEASE:Autosomal dominant and gene for (VWF) islocated on chromosome 12.VWF is synthesized by endothelial cells andmegakaryocyticIt acts as carrier protein for factor VIII which it isnon-covalently bound. A defect therefore leads todecreased plasma factor VIII level.It forms bridges b/w platelets and sub endotheliumeg collagen allowing platelets to adhere to damagedvessel walls. There fore defect of VWF leads toprolong bleeding after minor trauma.
QUALITATIVE PLETELET DISORDERQUALITATIVE PLETELET DISORDERVON-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 usuallyraise 3 in 30-90 minutes MASSIVE HAEMORRHAGES:
COAGULATION DISORDER:COAGULATION DISORDER:Coagulation factor disorder can either caneither arise from single factor usually“congenital deficiency” eg factor VIIIresulting in HAEMOPHILIA-A ormultiple factor which is acquired eg Sec:to liver disease or warfarin therapy.
HEAMOPHILIA – A (CLASSIC TRUEHAEMOPHILIA)HAEMOPHILLIA – B (CHRISTMASDISEASE)COAGULATION DISORDER:COAGULATION DISORDER:CONGENITAL BLEEDINGCONGENITAL BLEEDINGDISORDER:DISORDER:
HEAMOPHILIA – A (CLASSIC TRUEHEAMOPHILIA – A (CLASSIC TRUEHAEMOPHILIA)HAEMOPHILIA) X-linked disorder Due to defect of factor VIIIC/F: Bleeding occurs as bruising when babies are about 6 monthold.Trauma results in excessively bleeding. Recurrent bleeding hemorrhage at following sitesknee, elbow, ankle, and hip. Mucus membrane internal bleeding of mouth, lips, gums,brain and kidney Muscle haematoma esp. calf and Psoas muscleRx Factor VIII infusion
HAEMOPHILLIA – B (CHRISTMASHAEMOPHILLIA – B (CHRISTMASDISEASE)DISEASE) Due to deff: of factor IXS/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
DISSAMINATED INTRAVASCULARDISSAMINATED INTRAVASCULARCOAGULATIONCOAGULATION DIC is condition characterized by thrombosis withincirculation. DIC can be induced by variety of differentmechanism. Endothelial cell damage eg endotoxic in G –ve septicemiaresults in tissue factor release which in turn leads tocoagulation cascade through extrinsic pathway. The presence thromboplastin from damaged tissue,placenta, fat embolus/following brain injury may activatecoagulation This results in consumption of platelets and coagulationfactors which secondarily activation of fibrinolysis leadingto bleeding tendency.
DICDIC::CAUSESInfectious: E Coli Nessieria meningitis Strep pneumonia MalariaObstetric RPOC Abruptio placentae Amniotic fat embolisms Pre-eclampsiaCancer Lung Pancreas ProstateCLINICAL FEATURES:Bleeding, thrombosis, bleedingfar from common thanthrombosis.Subacute DIC:Occurs primarily in cancerouspts results in superficial + deepvenous thrombosis.Other Manifestation:High incidence of cardiorespiratory failure
DICDICLAB:ThrombocytopeniaProlong PTAPPTT may benormal/increasedLow fibrinogenIncreased level D-dimmer
Treatment of DICTreatment of DICRx 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 plasmafibrinogen level above 150 mg/dl FFP When thrombosis i-e DVT, Pulmonary their give Heparin.