Coagulation factors: disorders due to clotting factor deficiency: MEDICINE 💊 HEMOPHILIA-A 💊 HEMOPHILIA-B 🍃LAB DIAGNOSIS 🍃CLINICAL FEATURES 🍃TREATMENT

1. DISORDERS DUE TO
CLOTTING FACTOR
DEFICIENCIES

2. CLOTTING FACTOR
Clotting factors are proteins in the
blood that control bleeding.

3. CLOTTING FACTOR DEFICIENCIES
•If any of the clotting factors is missing
or is not working properly, the
coagulation cascade is blocked.
•When this happens, the blood clot does
not form and the bleeding continues
longer than it should.
•Deficiencies of factor VIII and factor IX

4. •Rare clotting factor deficiencies are bleeding
disorders in which one or more of the other
clotting factors (i.e. factors I, II, V, V+VIII,VII,
X, XI, or XIII) is missing or not working
properly.
•Less is known about these disorders because
they are diagnosed so rarely.
•In fact, many have only been discovered in
the last 40 years.

5. COAGULATION DISORDER
•These are a group of disease caused due to
deficiency of clotting factors and lead to
defects in normal clot formation process
Classification:
Based on origin these disorder are of 2 types:
1.Hereditary coagulation disorder
2.Acquired coagulation disorder

6. HEREDITARY COAGULATION DISORDER
•These inherited plasma coagulation disorders are
due to qualitative or quantitative defect in single
coagulation factor.
A. Sex Linked (X) Disorders
•e.g. Classical haemophilia or haemophilia A,
Christmas disease or haemophilia B
B. Autosomal Disorders
•e.g. von Willebrand's disease

7. CLASSICAL HAEMOPHILIA
•It is the second most common cause of hereditary
coagulation disorder.
•lt is inherited as sex (X) linked recessive trait, so
more common in males while females are the
carriers.

8. PATHOGENESIS
•Quantitative reduction in factor VIII (in 90% of
cases).
•Normal or increased level of factor VIII with
reduced activity (in 10% of cases).

9. CLINICAL FEATURES:
•Symptoms are elicited when factor VIll activity is
reduced to less than 25%.
•Patient suffers bleeding for hours to days and severity
is based on plasma level of factor VIlI activity.
•Recurrent painful haemarthroses and muscle
hematoma and sometimes haematuria.

10. Lab diagnosis
•Whole blood coagulation time is raised in severe cases only.
•Prothrombin time is usually normal.
•Activated partial thromboplastin time (APTT or PTTK) is
typically prolonged.
•Specific assays for factor VIlI shows lowered activity (50%
activity of factor VIII in female carriers).
Treatment:
•Factor VIll replacement therapy

11. CHRISTMAS DISEASE/HAEMOPHILIA B
• X linked recessive disease.
• Rarer than haemophilia A.
• Incidence Ratio is 1: 100000 male birth.
• Inheritance pattern and clinical features are similar to classical haemophilia.
Lab Diagnosis:
• Assay of factor IX level which is lowered. Other lab findings are similar to
haemophilia A.

12. TREATMENT
•Infusion of fresh frozen plasma or plasma enriched
with factor IX.

13. VON WILLEBRAND'S DISEASE
•Most common hereditary coagulation disorder.
•Inherited as autosomal dominant trait.
•Incidence rate is 1:1000 of either sex.
•Occurs due to qualitative or quantitative defect in VWF.
Clinical Features:
•Spontaneous bleeding from mucous membranes,
excessive bleeding from nose and menorrhagia.

14. Lab Diagnosis:
•Prolonged bleeding time.
•Normal platelet count.
•Reduced plasma WF concentration.
•Defective platelet aggregation with ristocetin, an antibiotic.
•Reduced factor VIll activity.
Treatment:
•Cryo-precipitates or Factor VIII concentrates

15. ACQUIRED COAGULATION
DISORDER
•These are characterized by deficiency of multiple
coagulation factor.
•Vitamin K deficiency
•Coagulation disorder of liver disease
•Fibrinolytic detects
•Disseminated intravascular resistance.

16. VITAMIN K DEFICIENCY
•Vitamin K serves as a cofactor in the formation of 6 prothrombin
complex proteins (Vitamin K dependent coagulation factors)
synthesized in the liver: Factor II, VII, IX, X, Protein C and Protein S.
Causes of Vitamin K deficiency
•Obstructive jaundice.
•Chronic diarrhoea.
•Liver disease.
•Haemorrhagic states in infants.

17. LAB DIAGNOSIS:
• PROLONGED PTT AND PTTK.
TREATMENT:
• PARENTERAL ADMINISTRATION OF VITAMIN K CAUSES
COMPLETE RECOVERY IN 48 HRS.

18. COAGULATION DISORDER IN LIVER DISEASE
LIVER IS THE SITE OF SYNTHESIS AND METABOLISM
OF COAGULATION FACTORS.
Factors promoting coagulation
• Synthesis of Coagulation
Factors.
CLEARANCE OF FIBRINOLYTIC ENZYMES CLEARANCE
OF ACTIVATED FACTORS LIVER DISEASE LEADS TO
HYPERCOAGULABILITY AND PREDISPOSE TO DEVELOP
DIC AND SYSTEMIC FIBRINOLYSIS.
Factors inhibiting coagulation
• Synthesis of Anti-thrombin 3,
Protein C and Protein S

19. Major causes of bleeding in liver disease
are:
• Morphologic lesions:
Portal hypertension, peptic ulceration, gastritis.
• Hepatic dysfunction:
Impaired hepatic synthesis of coagulation factors and coagulation
inhibitors, impaired absorption and metabolism of Vitamin K, failure
to clear activated coagulation factors.

20. •Complication of therapy
Massive transfusion leading to platelet and
clotting factors dilution, following heparin therapy.
Lab Diagnosis:
Prolonged PTT and PTTK, mild
thrombocytopenia, normal fibrinogen level and
decreased hepatic stores of Vitamin K.

21. DISSEMINATED INTRAVASCULAR
COAGULATION
Also called as defibrinate syndrome or consumption coagulopathy
is a complex thrombo-haemorrhagic disease occurring as
secondary complication of some systemic disease.
Major disorders associated with DIC:
•Obstetrics Complications- Abruption placentae, retained dead
foetus, septic abortion, amniotic fluid embolism, toxaemia.
•Infections- Gram negative sepsis, meningococcemia, rocky
mountain spotted fever, malaria.

22. •Neoplasms- Carcinoma of pancreas, prostate, lung and
stomach.
•Massive Tissue Injury- Traumatic, burns, extensive
surgery.
•Miscellaneous- Acute intravascular haemolysis, snake
bite, giant haemangioma, shock, heat stroke.

23. Clinical Features:
•Widespread fibrin deposition within microcirculation
leading to ischemia of organs like kidney and brain.
•Bleeding diathesis- ensues as the platelets and
clotting factors are consumed and there are
secondary release of plasminogen activator but
also digest Factor V and VIlI there by reducing their
concentration further.

24. Lab Diagnosis:
•Reduced platelet count.
•Blood film shows microangiopathic hemorrhagic haemolytic
anaemia.
•Plasma fibrinogen level is reduced.
Treatment:
•Anticoagulants like heparin or coagulants contained in fresh
frozen plasma, underlying disorder must be treated
simultaneously.

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