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Haemostasis &Bleeding disorders

Haemostasis

Introduction: Road map..

Haemostasis capacity to minimise loss of blood following injury to blood vessel. Blood vessel Coagulation Platelet act. Bleeding disorders Bv, Plt, Coag. Laboratory tests of Haemostasis. BT, CT, PT, aPTT, TT, FDP. Factor analysis, PLT function, PCR
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Haemostasis overview:
BV Injury
Contact/ Tissue Factor

Neural

Blood Vessel Constriction

Platelet Aggregation Primary hemostatic plug Platelet Activation

Coagulation Cascade

Reduced Blood flow

Fibrin formation

Stable Hemostatic Plug

Haemostasis

Classification:

Disorders of Blood vessels


Disorders of Platelets

Disorders of Coagulation
Other disorders

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Thrombocytopenia

Haemostasis

Blood Vessels in Hemostasis:

Initial phase of hemostasis. Present as petechiae / ecchymoses Simple easy bruising women Senile purpura atrophy, Scurvy vit-C deficiency, collagen def. Steroid induced purpura Henoch-Schonlein children, viral fevers.

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Thrombocytopenia

Haemostasis

Coagulation:

Fibrinogen to Fibrin Coag. Cascade Several factors proenzymes-activation. Enzyme amplication Plasma, Endothelium & Platelets Stable hemostatic plug. Clot lysis starts soon after clot formation.
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Haemostasis

HEMOSTASIS

Primary Hemostasis

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

Tertiary Hemostasis

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Haemostasis:

Vasoconstriction N Platelet activation Haemostatic plug Coagulation Stable clot formation Clot dissolution

Coagulation:

Contact activationIntrinsic system Tissue factor activation Extrinsic Common pathamplification Fibrin formation Fibrin lysis.

Coagulation Cascade:
Intrinsic Pathway (Contact) (12,11,9,8) (aPTT) (Factor 10) Common Path (5,2) (Thrombin) (TT) Extrinsic Path Tissue - (7) (PT)

Fibrinogen Fibrin

(F & FDP)

Haemostasis

Disorders of Hemostasis

Vascular disorders

Scurvy, easy bruising,


Low Number or abnormal function Factor deficiency.

Platelet disorders

Coagulation disorders

Mixed/Consumption: DIC

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Thrombocytopenia

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Haemostasis

Bleeding: Clinical Features


1. 2. 3. 4.

Local - Vs - General, spontaneous . . Hematoma & Joint bleed - Coagulation Skin/Mucosal Petechiae & Purpura PLT wound / surgical bleeding Immediate - (PLT) Delayed - (Coagulation)

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Thrombocytopenia

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Haemostasis

Coagulation disorders:
Deficiencies of Clotting factors Onset - delayed after trauma Deep bleeding

Into joints - Hemarthroses Into deep tissues Hematoma large skin bleed Ecchymoses

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Thrombocytopenia

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Haemostasis

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


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Haemostasis

Factor VIII Deficiency

Classic hemophilia (hemophilia A) X-linked disorder (affects 1 males) Most common - severe bleeding Spontaneous hematomas Abnormal aPTT Intrinsic path. Diagnosis - factor VIII assay Treatment - factor VIII concentrate Cryoprecipitate (less desirable)

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Thrombocytopenia

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Haemostasis

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

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Thrombocytopenia

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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
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Secondary Hemostatic Disorders

Haemostasis

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Thrombocytopenia

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Haemostasis

Haemophilia

Congenital deficiency -Factor 8 (A) or 9 (B) Bleeding Haematoma, joint etc. Gene on X chromosome.

(Carrier females, Males suffer)

Prolonged PTT but normal PT. FFP or Factor replacement Life long.

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Thrombocytopenia

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Platelet Disorders Features:

Haemostasis

Mucocutaneous bleeding Petechiae, Purpura, Ecchymosis. spontaneous bleeding after trauma CNS bleeding (severe plt) Prolonged bleeding time (BT)
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Haemostasis

Disorders of platelets

Decreased Number: Thrombocytopenia


Defective Platelet function:


Decreased Production Decreased Survival Immune (ITP) Increased utilization - DIC Acquired Drugs Aspirin, MPS, MDS Congenital Eg. Thrombasthenia.

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Thrombocytopenia

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Haemostasis

Platelet dysfunction:
Inherited Disorders: Bernard-Soulier disease

large platelets, failure of adhesion normal size, failure of aggregation

Glanzmanns thrombasthenia

Acquired Disorders: Drugs - Aspirin, Alcohol, Uremia,


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Haemostasis

Routine Investigations:

Bleeding time BV, PLT

Clotting time inaccurate 10-20min Prothrombin time Extrinsic (2,5,10 + 7),


aPTT Intrinsic (2,5,10 + 8,9,12)

ivy template method - 3-8min

Acquired diseases, liver dis, warfarin therapy Haemophilia, Congenital. DIC & Heparin therapy.

Trombin Time: Fibrinogen (common path)


CBC Plt Count FDP Fibrinogen Degradation Products - DIC

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Thrombocytopenia

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Haemostasis

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
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BLEEDING TIME vs. PLATELET COUNT


400 350 300 250 200 150 100 50 0 3.5 4 4.5 5 5.5 7 Minutes
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Haemostasis

Platelet count (x 1000)

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Haemostasis

Platelet Aggregation Curves

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Thrombocytopenia

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Disseminated Intravascular Coagulation Major pathologic processes obstetric complications, neoplasms, infection (sepsis), major trauma Primary - platelet consumption ( bleeding time, platelets) Secondary - factor consumption 30 ( PT, aPTT)
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Combined Primary and Secondary Hemostatic Disorders (DIC)

Haemostasis

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Severe Liver Disease Primary - dysfunctional platelets and/or thrombocytopenia ( BT) Secondary - decrease in all coagulation factors except vWF ( PT, aPTT) Vitamin K will promote synthesis of factors II, VII, IX, X
Thrombocytopenia

Combined Primary and Secondary Hemostatic Disorders

Haemostasis

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Summary Hemostatic Disorders

Haemostasis

BT Plt PT PTT
Vascular Dis PLT Disorder - - - -

Factor 8/9 *Congenital


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Haemostasis

Summary
Symptom Petechiae Sites Time Ecchymoses /Hematomas Platelet Yes Skin & Mucosa Immediate Yes Coagulation No Deep Tissue Delayed Yes

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Haemostasis

Special Investigations:

Specific Factor Assays Platelet function studies


Electrophoresis Bone marrow examination plt Molecular Biology FISH

Aggregometry, Adhesion studies Immuno-fluorescence

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Thrombocytopenia

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Haemostasis overview:
BV Injury

CBC-Plt BT,(CT) PT, PTT,TT Contact/ Special tests


Tissue Factor

Haemostasis Lab Tests

Neural

Blood Vessel Constriction

Platelet Aggregation Primary hemostatic plug Platelet Activation

Coagulation Cascade

Reduced Blood flow

Fibrin formation

Bl. Disorders:
Stable Hemostatic Plug
1/5/2014 Thrombocytopenia

Cong/Acqured BV, Coag, PLT


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Haemostasis

Nail bed - Hematoma


Red Blue/Gr Brown

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Thrombocytopenia

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Haemostasis

Contusion - Hematoma

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Thrombocytopenia

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Platelet Coagulation

Petechiae, Purpura

Hematoma, Joint bl.

Haemostasis

Petechiae & Echymoses -Plt

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Haemostasis

Petechiae & Echymoses -Plt

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Thrombocytopenia

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Haemostasis

Bleeding-Coagulation disorder
Deep bleeding Haematoma Joint bleeds Haemophilia

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Thrombocytopenia

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Haemostasis

Sub Conjuctival Haemorrhage


Low PLT

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Thrombocytopenia

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Dengue Hemorrhagic fever Plt

Haemostasis

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Thrombocytopenia

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Haemostasis

Petechiae in Vasculitis
(Rocky Mountain Spotted Fever)
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Haemostasis

Henoch-Schonlein purpura

Immune disorder Children Follows infection Petechiae with edema and itching.

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Thrombocytopenia

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Haemostasis

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Thrombocytopenia

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Haemostasis

Dengue Hemorrhagic fever

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Thrombocytopenia

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