Disorders of Coagulation, Pathology, 4th Year MBBS

1. DR.UMME HABIBA
ASSISTANT PROFESSOR HAEMATOLOGY

2.  Review of normal Hemostasis.
 Tests For Coagulation Disorders.
 Introduction to coagulation disorders
 Hemophilia A
 Hemophilia B
 Disseminated Intravascular Coagulation
 vWD

3.  Primary hemostasis: local vasoconstriction & platelet plug
formation
 Coagulation cascade: To reinforce & stabilize platelet plug
 Fibrinolysis

6.  The process of dissolution of clot & removal of fibrin is known as fibrinolysis.

7.  I. Fibrinogen
 II. Prothrombin
 III. Thromboplastin
 IV. Calcium++
 V. Proaccelerin/Labile Factor
 VII. Proconvertin/Stable Factor
 VIII. AHF (Anti-Hemophilic Factor)
 IX. AHF ß (Christmas Factor)
 X. Staurt-Prower Factor
 XI. Plasma Thromboplastin antecedent
 XII. Hageman Factor
 XIII. Fibrin- Stabilizing Factor
 HMWK. Fitzgerald Factor

10.  Hemophilia A & B-classic examples of Inherited (x-linked recessive)
 DIC- consumptive coagulopathy, acquired.
 Vitamin K deficiency (II,VII,IX,X).
 Liver Disease(coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX,
X, XI, XII, XIII, as well as protein C, protein S and antithrombin).
 Von Willibrand disease.(vWF)

11. Screening Test Abnormalities Indicated by
Prolongation
Most Common Cause
Thrombin Time TT Deficiency/Abnormality of
Fibrinogen/ Inhibition of
Thrombin by Heparin/ FDPs
DIC
Heparin Therapy
Prothrombin Time PT Deficiency/Acquired Inhibitor of
one or more of: II,V,VII,X and
Fibrinogen
Liver Disease
Warfarin Therapy
DIC
Activated Partial
Thromboplastin Time aPTT
Deficiency/Acquired Inhibitor of
one/more of: XII,XI,IX, VIII, X,V,
II, Fibrinogen
Hemophilia
Christmas Disease
(+conditions Above)
Fibrinogen Quantitation Fibrinogen Deficiency DIC
Liver Disease

13.  Hereditary blood- coagulation disorders in which the blood fails to clot normally because
of a deficiency or abnormality of one of the clotting factors.
 X-linked recessive, mostly occurred in males.
 Lack of formation of prothrombin activator
 1. Deficiency of factor VIII(hemophilia A)- severe
 2. Deficiency of factor IX(hemophilia B/Christmas Disease)-moderate
 3. Deficiency of factor XI (hemophilia C)-mild
 4. Deficiency of factor V (parahemophilia)
 1/5,000 male births
 1 per 10,000 population
 85 % - F VIII deficiency
 10- 15 % - F IX deficiency
 Hemophilia A: B ratio= 7:1

15.  Factor VIII participates in blood coagulation; it is a cofactor
for factor IXa, which, in the presence of Ca2+ and phospholipids,
forms a complex that converts factor X to the activated form Xa.
 Partial or complete deficiency of factor VIII leads to Hemophilia A.
 In case of vWF deficiency(von Willibrand Disease), there is
functional deficiency of Factor VIII (as vWF binds to VIIIF and is
important in platelet adhesion)

16.  Coagulation Factor IX is an important enzyme in the process of
hemostasis and normal blood clotting as it plays a key role within
the coagulation cascade by converting X to Xa in the presence of
cofactor viii and calcium.
 Partial or complete deficiency of IX leads to hemophilia B or
Christmas disease.

18.  External bleeding :
 Prolonged Bleed in the mouth
from a cut or bite or from cutting
or losing a tooth.
 Nosebleeds for no obvious reason.
 Heavy bleeding from a minor cut.
 Bleeding from a cut that resumes
after stopping for a short time.
 Internal bleeding :
 Hemarthrosis: Joint bleed
 Blood in the urine (from bleeding
in the kidneys or bladder).
 Blood in the stool (from bleeding
in the intestines or stomach).
 Large bruises (from bleeding into
the large muscles of the body).

19.  Bleeding in the Joints
 Bleeding in the knees, elbows, or
other joints is another common
form of internal bleeding in people
who have hemophilia.
 The bleeding causes tightness in
the joint with no real pain or any
visible signs of bleeding.
 The joint then becomes swollen,
hot to touch, and painful to bend.

20. Test Result
PT Normal
aPTT Prolonged
Platelet Count Normal
Bleeding Time Normal
Factor Assay Reduced activity of factor VIII (hemophilia A)
Reduced activity of factor IX (hemophilia B)

21.  Supportive.
 Specific Factor Replacement.

23.  DIC is an acquired coagulopathy characterized by both thrombosis
& hemorrhage.
 DIC is a clinic-pathologic syndrome of activated coagulation that
manifests with bleeding or thrombosis.
 Patients with DIC have a loss of balance between the clot-promoting
and lysing systems in vivo.
 This syndrome can have a clinical spectrum ranging from bleeding
to a pro-thrombotic state.
 DIC is not a specific(primary) diagnosis, and its presence always
indicates another underlying disease.
 Bleeding associated with DIC usually results from excess
fibrinolysis; thrombosis associated with DIC results from excess
thrombin formation.

27.  ACUTE DIC:
 Develops rapidly (hours-days)
 Intrinsic Pathway initiation by
endothelial damage
 Manifest as Hemorrhagic event
 Excessive clotting in small vessels
 Hypoperfusion of vital organs,
Petechiae, ecchymosis
 Associated with sepsis, amniotic fluid
embolism, anaphylaxis etc.
 CHRONIC DIC
 Slow activation of activation of
hemostatic system
 Spontaneous bruising rather than major
bleeds
 Manifest as prothrombotic conditions
 Chronic compensated DIC can continue
for many years – usually associated
with vascular malformations,
malignancies like mucinous
adenocarcinomas, retained dead fetus.

28.  Bleeding from venepuncture sites or wounds .
 May be generalized bleeding in the gastrointestinal tract, the oropharynx,
into the lungs, urogenital tract and in obstetric cases, per vaginal bleeding
may be particularly severe.
 Less frequently, microthrombi, may cause skin lesions, renal failure,
gangrene of the fingers or toes or cerebral ischemia.
 Some patients may develop subacute or chronic DIC, especially with
mucin‐secreting adenocarcinoma.
 Ecchymosis, Trousseau's sign,
 Chronic may go on to acute

29. TEST ABNORMALITY
Platelet Count Decreased
Bleeding Time Prolonged
FDP Increased
Factor Assay Decreased
PT Prolonged
aPTT Prolonged
Thrombin time,Clotting Time Prolonged
Fibrinogen Decreased
D-dimer Increased
Antithrombin Decreased

30.  Present as thrombotic event.
 Connective tissue disorders, including those with giant cavernous
hemangiomas (who may have bleeding manifestations)
 Chronic renal disease
 venous thrombosis, pulmonary embolus, and marantic endocarditis
with or without arterial embolization, can present with thrombosis
secondary to activated coagulation and increased thrombin
formation.

31. TEST ABNORMALITY
Platelet Count Slightly Decreased/within reference range
FDP Slightly Increased
PT Prolonged/normal
aPTT Prolonged/normal
Fibrinogen Decreased Modestly
D-dimer Slightly Increased

32.  Treat the underlying cause.
 Anticoagulants.
 Replacement therapy (for factors/ platelets etc)
 Supportive.

34.  von Willibrand factor
 Synthesis in endothelium and megakaryocytes
 Forms large multimer
 Carrier of factor VIII
 Anchors platelets to subendothelium
 Bridge between platelets
 Presents most commonly as platelet-type bleed (i.e. bleeding disorder)
 1% prevalence, most common bleeding disorder
 Spontaneous & wound bleeding, mucocutaneous bleed.
 Usually Autosomal Dominant inheritance.
 Prolonged BLEEDING TIME, Normal platelet count
 vWF is defective in von Willibrand disease
 Usually BOTH platelet-type and Factor VIII-vWF disorders are present

36. Type 1 vWD Type 2 vWD Type 3 vWD
Most common 75-80% Less common 15-20% Rare(1:500,000)
Autosomal Dominant Autosomal Dominant Autosomal recessive
Quantitative deficiency
(reduced vWF)
Qualitative defect
(dysfunctional vWF)
Absent vWF
Mild Mild to moderate Severe, present in early
childhood
Desmopressin is effective Desmopressin not effective

37. Assay Type 1 vWD Type 2 vWD Type 3 VWD
vWF antigen  Normal 
vWF activity   
Multimer analysis Normal Normal Absent

38.  Cryoprecipitate
 Source of fibrinogen, factor VIII and VWF
 Only plasma fraction that consistently contains VWF multimers
 DDAVP (deamino-8-arginine vasopressin)
  plasma VWF levels by stimulating secretion from endothelium
 Duration of response is variable
 Not generally used in type 2 disease
 Dosage 0.3 µg/kg q 12 hr IV
 Factor VIII concentrate (Intermediate purity)
 Virally inactivated product

39.  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 FFP, Vitamin K

40. Attempt all as a part of your assignment

41.  Hemophilia A
 Hemophilia B
 Parahemophilia
 Hemophilia C

42.  Factor V
 Factor VIII
 Factor IX
 Factor XI

43.  Type 1 Von Willibrand Disease
 Hemophilia A
 Hemophilia C

44.  Type 1 vWD
 Type 2 vWD
 Type 3 vWD

45. Write in Comment box.