Bleeding desorder -shiv

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BLEEDING DISORDERS : 

BLEEDING DISORDERS Email: Shivaprakashsosale@gmail.com +91-7204776479 SAPTHAGIRI INSTITUTE OF MEDICAL SCIENCES(SIMS), BENGALURU . DR.SHIVAPRAKASH SOSALE CHANDRASHEKAR MBBS,MD(Paediatrics) SInCHE …..Reaching unreached

Hemostasis-basics : 

Hemostasis-basics To maintain blood in fluid state Rapid n localised hemostatic plug at the site of vascular # Normal hemostasis depends on delicate balance b/w Blood vessels Platelets Coagulation cascade Inhibitors Fibrinolytic system

Classic haemostatic machanism; : 

Classic haemostatic machanism; Vascular response Platelet adhesion Platelet aggregation Clot formation Clot stabilisation Limiting to site of # by anticoagulents Re-establishment of vasculature by fibriolysis and vascular healing

Hemostasis : 

Hemostasis BV Injury Platelet Aggregation Platelet Activation Blood Vessel Constriction Coagulation Cascade Stable Hemostatic Plug Fibrin formation Reduced Blood flow Damage/contact. Primary hemostatic plug Neural CBC-Plt BT,(CT) PT PTT Platelet study Antibody tests Factor Assay Contact

Slide 6: 

Clotting

HEMOSTASIS : 

HEMOSTASIS Primary Hemostasis Blood vessel contraction Platelet Plug Formation Secondary Hemostasis Activation of Clotting Cascade Deposition & Stabilization of Fibrin Tertiary Hemostasis Dissolution of Fibrin Clot Dependent on Plasminogen Activation

Classification: : 

Classification: Disorders of Blood vessels Scurvy, senile purpura, Henoch-Schonlein syndrome. Disorders of Platelets Thrombocytopenia ITP, TTP, HUS, DIC. Aspirin therapy, Thrombasthenia, Disorders of Coagulation Extrinsic, intrinsic, combined. Other disorders Post transfusion purpura, MPS, MDS.

Platelet dysfunction: : 

Platelet dysfunction: Inherited Disorders: Bernard-Soulier disease large platelets, failure of adhesion Ab vwf receptor(GPIb complex)on platelet membrane Thrombocytopenia ,gaint plt,BT>20min Glanzmann’s thrombasthenia normal size, failure of aggregation Def .of plt- fibrinogen receptor GPIIb-IIIa Plt size ,count n morphology N,BT inc Acquired Disorders: Drugs - Aspirin, Alcohol, Uremia,

Plt-storage granules def: : 

Plt-storage granules def: Dense body def-absent granules that contain ADP,ATP,Ca2+,serotonin Gray platelet syndrome-absent plt alfa granules

Kasabach-marritt synd : 

Kasabach-marritt synd Gaint hemangioma w localised intravascular coagulation causing thrombocytopenia n hypofibrinogemia Inside hemangioma-plt trapping n activation of coagulation w fibrinogen consuption w generation of FDP A-V malformation within lesion can cause heart failure RX –surgery,lasar,steriod,radiation ,ifn

Congenital thrombocytopenic synd; : 

Congenital thrombocytopenic synd; Cong.amegakaryocytic thrombocytopenia; Only skin n mucous memb –petechie n purpura Bone marrow-ab megakaryocytes Mutaton in stem cell TPO receptor BT curative

TAR : 

TAR Thrombocytopenia B/l radial anamalies Intolerence to cow s milk formula(50%) Eosinophilia n leukemoid reaction AR

WAS(wiskott aldrich synd) : 

WAS(wiskott aldrich synd) Thrombocytopenia w tiny platelets Eczema Rec.infection XR 5% pts develop lymphoreticular malignancies BMT curative

OTHERS; : 

OTHERS; SEBASTIAN SYND EPSTEIN SYND MAY-HEGGLIN SYND FECHTNER SYND

Platelet Coagulation : 

Platelet Coagulation Petechiae, Purpura Hematoma, Joint bl.

Platelet Disorders - Features: : 

Platelet Disorders - Features: Mucocutaneous bleeding Petechiae, Purpura, Ecchymosis. spontaneous bleeding after trauma CNS bleeding (severe  plt) Prolonged bleeding time (BT)

Idiopathic Thrombocytopenic Purpura (ITP) : 

Idiopathic Thrombocytopenic Purpura (ITP) Acute - children (post infection) Chronic - adults ( females, 20-40 yrs) autoimmune disorder antiplatelet antibodies (IgG) IgG coated platelets removed by spleen Usually  megakaryocytes in BM H/O viral illness 50-60% -EBV,HIV

C/F-1to4 yr-sudden onset petechiae n purpura : 

C/F-1to4 yr-sudden onset petechiae n purpura Splnomegaly rae Spontaneous resolution 70-80%cases present w Ac.ATP <1%pt present w intracranial hemorrhage 20% pts w Ac. ATP go on to have Cr.ATP LAB-Hb, WBC,DC normal In adolescents w new onset ITP ANA to be done to r/o SLE

Vascular disorders: : 

Vascular disorders: Petechiae, purpura, ecchymoses senile purpura vitamin C deficiency (scurvy) Connective tissue disorders Infections – Meningococcus Henoch-Schonlein Purpura-Immu

Henoch-Schonlein purpura(anaphylactoid purpura) : 

Henoch-Schonlein purpura(anaphylactoid purpura) Immune disorder Children Follows infection Small vessel Petechiae with edema and itching. IgA &C3

Henoch-Schonlein purpura : 

Henoch-Schonlein purpura 15y Male, fever, painful symmetric polyarthritis for a day. During the next two days, edema and palpable purpura developed.

Slide 25: 

Pinkish maculopapular rash-blanch on pressure> palpable purpura Local angioedema Arthritis GIT-diarrhea,pain,ocult blood in stool, Hepatosplenomegaly,LNP Renal-hematuria ,proteinuria,--mesengial deposition of IgA,IgM,C3 & fibrin Difinitive Dsis-BIOpsy

TTP; : 

TTP; PENARD- 1) Fever 2) Microangopthic hemolytic anemia 3) Thrombocytopenia 4) Ab. renal function 5) CNS changes Def of metalloprotein ADAMTS-13 Rx- Plasmaparesis,Steroids,Splenectomy

HUS : 

HUS MC Ac.renal failure in children Triad –1.microangiopathic hemolytic anaemia 2.Trombocytopenia 3.Uremia Etiology—bacterial,viral,drugs, granulomatous condition Pathology—Endothelial cell # C/F---preceded by GI infection

Slide 29: 

Diagnosis—microangiopathic hemolytic anaemia ,thrombocytopenia,ARF PS-Burr cell +,fragmented RBC, Retic inc, Coombs neg XR-Thumb printing colitis RX—plasmaparesis/FFP

Thrombocytopenia-TTP : 

Thrombocytopenia-TTP

Slide 31: 

Von-Willebrand Disease vWF: F-VIII & PLT function. Defective Platelet Adhesion Skin Bleeding Prolonged Bleeding time. Low Factor VIII levels.

Von-Willebrand Disease: : 

Von-Willebrand Disease: Coagulation + PLT disorder: Congenital disorder Deficiency of vWF molecule Part of FVIII, Mediates platelet adhesion Prolonged Bleeding time Low Factor VIII & long Aptt Mucocutaneous bleeding

Slide 33: 

Laboratory evaluation of von Willebrand disease Classification Type 1 Partial quantitative deficiency Type 2 Qualitative deficiency Type 3 Total quantitative deficiency Diagnostic tests: vonWillebrand type Assay 1 2 3 vWF antigen ß Normal ßß vWF activity ß ß ßß Multimer analysis Normal Normal Absent

VWD TYPE 1 : 

VWD TYPE 1 MC ,85% of cases Epistaxis ,bruising and menorrhagia Rx –Desmopressin-0.3microg/kg i.v intranasal(stimate)-150ug/kg <50kg 300ug/kg >50kg

VWD TYPE 2A (proteolysis) : 

VWD TYPE 2A (proteolysis) Abnormal proteolysis of VWF Only smallest VWF present RX-VWF replasement

VWF 2B (hyperactive) : 

VWF 2B (hyperactive) Mutations resulting in “hyperactive” VWF Binds spontaneously to platelets w rapid clearance of both Mod to severe thrombocytopenia+ Rx-infn vwf

VWD 2M(binding function) : 

VWD 2M(binding function) Mutation results in dec platelet binding function of vwf Level of vwf activity dec than vwf antigen

VWF 2N (autososmal hemophilia) : 

VWF 2N (autososmal hemophilia) Dec in factor VIII binding by vwf Binds weakly or not atall to factor VIII Results rapid clearence of factor VIII that weakly complexes to wvf So factor VIII level dec much more than vwf

VWD 3 : 

VWD 3 Undetectable level of vwf Measurable level of f VIII Ddavp no effective Can manifest joint or muscle bleeding simillar to hemophilia

PSEUDO (platelet type) VWD : 

PSEUDO (platelet type) VWD Abnormality of GPIb receptor on platelet In 2B VWD-GPIb receptor on platelet is hyperfunctional n binds plasma vwf spontaeously

Slide 41: 

Acquired desorders Vit k def Liver ds DIC

Slide 42: 

Vitamin K deficiency Source of vitamin K --- Green vegetables Synthesized by intestinal flora Required for synthesis--- Factors II, VII, IX ,X Protein C and S Causes of deficiency ---- Malnutrition Biliary obstruction Malabsorption Antibiotic therapy Treatment----- Vitamin K Fresh frozen plasma

Secondary Hemostatic Disorders : 

Secondary Hemostatic Disorders Acquired coagulation disorder: Vitamin K deficiency - neonates - decreased intestinal flora and dietary intake - oral anticoagulants (coumadin) - fat malabsorption syndromes Required for factors II, VII, IX, X Prolonged PT and aPTT

Slide 44: 

NOT AN INTERVAL

LIVER DZ : 

Decreased synthesis of II, VII, IX, X, XI, and fibrinogen Dietary Vitamin K deficiency (Inadequate intake or malabsortion) Dysfibrinogenemia Enhanced fibrinolysis (Decreased alpha-2-antiplasmin) DIC Thrombocytoepnia due to hypersplenism LIVER DZ

Slide 46: 

Common clinical conditions associated withDisseminated Intravascular Coagulation Sepsis Trauma Head injury Fat embolism Malignancy Obstetrical complications Amniotic fluid embolism Abruptio placentae Vascular disorders Reaction to toxin (e.g. snake venom, drugs) Immunologic disorders Severe allergic reaction Transplant rejection

DIC : 

Systemic activation of coagulation Intravascular deposition of fibrin Depletion of platelets and coagulation factors Bleeding Thrombosis of small and midsize vessels with organ failure DIC

DIC mechanism; : 

Coagulation Fibrinolysis Fibrinogen Fibrin Monomers Fibrin Clot (intravascular) Fibrin(ogen) Degradation Products Plasmin Thrombin Plasmin Release of thromboplastic material into circulation Consumption of coagulation factors; presence of FDPs  aPTT  PT  TT  Fibrinogen Presence of plasmin  FDP Intravascular clot  Platelets Schistocytes DIC mechanism;

Tests of Hemostasis: : 

Tests of Hemostasis: Screening tests: Bleeding.T - 10m. Platelet & BV function Prothrombin.T – Extrinsic, aPTT – Instrinsic Thrombin.T – common path. (DIC) Specific tests: Factor assays – hemophilia. Tests of thrombosis – TT, FDP, DDA, Platelet function studies: Adhesion, Aggregation, Release tests. Bone Marrow study

Coagulation disorders: : 

Coagulation disorders: Deficiencies of Clotting factors Onset - delayed after trauma Deep bleeding Into joints - Hemarthroses Into deep tissues – Hematoma large skin bleed – Ecchymoses

Slide 51: 

Blood Coagulation & Tests

Coagulation desorders : 

Coagulation desorders Congenital Hemophilia A(VIII) Hemophilia B(christmas ds) Hemophilia C(XI) Def .of contact factors(non-bleeding desorders) –XII,prekallikrein,HMWK Factor VII def. Factor X def. Factor II def (prothrombin) Fibrinogen def. Factor V def.(parahemophilia) Combined def factor V n VIII Factor XIII def (fibrin stabilising factor) vwd

Slide 54: 

CT- Large hematoma of psoas muscle

Coagulation Disorders : 

Coagulation Disorders Laboratory findings: Normal bleeding time & Platelet count Prolonged prothrombin time (PT) deficiencies of II, V, VII, X Prolonged time (aPTT) all factors except VII, XIII Mixing studies - normal plasma corrects PT or aPTT

Factor VIII Deficiency : 

Factor VIII Deficiency Classic hemophilia (hemophilia A) X-linked disorder (affects 1º males) Most common - severe bleeding Spontaneous hematomas < 1, 5, 75% Abnormal aPTT – Intrinsic path. Diagnosis - factor VIII assay Treatment - factor VIII concentrate Cryoprecipitate (less desirable)

Factor IX Deficiency : 

Factor IX Deficiency Christmas disease (Hemophilia B) X-linked recessive disorder Indistinguishable from classic hemophilia (F VIII) Requires evaluation of factor VIII and IX activity levels to diagnose Treatment - factor IX concentrate Cryoprecipitate if factor IX unavailable

Summary : 

Summary

Disorders of Hemostasis : 

Disorders of Hemostasis Vascular disorders – Scurvy, easy bruising, Henoch-Schonlein purpura. Platelet disorders Quantitative - Thrombocytopenia Qualitative - Platelet function disorders – Glanzmans Coagulation disorders Congenital - Haemophilia (A, B), Von-Willebrands Acquired - Vitamin-K deficiency, Liver disease Mixed/Consumption: DIC

Summary Hemostatic Disorders : 

Summary Hemostatic Disorders BT Plt PT PTT Vascular Dis -  - - - PLT Disorder -  -  - - Factor 8/9 *Congenital - - -  Vit K / Liver *Acquired - -  - Combined (DIC)   - 

Summary : 

Summary Complex system to keep blood fluid To block leakage on injury. BV, PLT & Coagulation Complex inhibitory mechanisms Complex thrombolysis mechanisms. Screening tests: BT, CT (PT, aPTT) Special tests: Factor assay, PLT function etc.

SAPTHAGIRI INSTITUTE OF MEDICAL SCIENSES BENGALURU. : 

SAPTHAGIRI INSTITUTE OF MEDICAL SCIENSES BENGALURU. Thank you SInCHE …..Reaching unreached