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
Thrombocytopenia 2

1/5/2014

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

1/5/2014

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.

1/5/2014

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.
Thrombocytopenia 6

1/5/2014

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
Thrombocytopenia 7

Secondary Hemostasis

Tertiary Hemostasis

1/5/2014

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

1/5/2014

Thrombocytopenia

15

15

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)

1/5/2014

Thrombocytopenia

16

16

Haemostasis

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

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

1/5/2014

Thrombocytopenia

17

17

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

Thrombocytopenia 18

1/5/2014

18

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)

1/5/2014

Thrombocytopenia

19

19

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

1/5/2014

Thrombocytopenia

20

20

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
21

Secondary Hemostatic Disorders

Haemostasis

1/5/2014

Thrombocytopenia

21

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.

1/5/2014

Thrombocytopenia

22

22

Platelet Disorders Features:

Haemostasis

Mucocutaneous bleeding Petechiae, Purpura, Ecchymosis. spontaneous bleeding after trauma CNS bleeding (severe plt) Prolonged bleeding time (BT)
1/5/2014 Thrombocytopenia 23

23

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.

1/5/2014

Thrombocytopenia

24

24

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,

1/5/2014 Thrombocytopenia 25

25

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

1/5/2014

Thrombocytopenia

26

26

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
Thrombocytopenia 27

1/5/2014

27

BLEEDING TIME vs. PLATELET COUNT

400 350 300 250 200 150 100 50 0 3.5 4 4.5 5 5.5 7 Minutes
1/5/2014 Thrombocytopenia

Haemostasis

Platelet count (x 1000)

12

15

25

30

28

28

Haemostasis

Platelet Aggregation Curves

1/5/2014

Thrombocytopenia

29

29

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)
1/5/2014 Thrombocytopenia 30

Combined Primary and Secondary Hemostatic Disorders (DIC)

Haemostasis

1/5/2014

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

31

31

Summary Hemostatic Disorders

Haemostasis

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

Factor 8/9 *Congenital

1/5/2014

Thrombocytopenia

32

32

Haemostasis

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

1/5/2014

Thrombocytopenia

33

33

Haemostasis

Special Investigations:

Specific Factor Assays Platelet function studies

Electrophoresis Bone marrow examination plt Molecular Biology FISH

Aggregometry, Adhesion studies Immuno-fluorescence

1/5/2014

Thrombocytopenia

34

34

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

35

35

Haemostasis

Nail bed - Hematoma

Red Blue/Gr Brown

1/5/2014

Thrombocytopenia

36

36

Haemostasis

Contusion - Hematoma

1/5/2014

Thrombocytopenia

37

37

Platelet Coagulation

Petechiae, Purpura

Hematoma, Joint bl.

Haemostasis

Petechiae & Echymoses -Plt

1/5/2014

Thrombocytopenia

39

39

Haemostasis

Petechiae & Echymoses -Plt

1/5/2014

Thrombocytopenia

40

40

Haemostasis

Bleeding-Coagulation disorder
Deep bleeding Haematoma Joint bleeds Haemophilia

1/5/2014

Thrombocytopenia

41

41

Haemostasis

Sub Conjuctival Haemorrhage

Low PLT

1/5/2014

Thrombocytopenia

42

42

Dengue Hemorrhagic fever Plt

Haemostasis

1/5/2014

Thrombocytopenia

43

43

Haemostasis

Petechiae in Vasculitis
(Rocky Mountain Spotted Fever)
1/5/2014 Thrombocytopenia 44

44

Haemostasis

Henoch-Schonlein purpura

Immune disorder Children Follows infection Petechiae with edema and itching.

1/5/2014

Thrombocytopenia

45

45

Haemostasis

1/5/2014

Thrombocytopenia

46

46

Haemostasis

Dengue Hemorrhagic fever

1/5/2014

Thrombocytopenia

47

47