patho

1. Dr. Ramesh Dhakhwa, MD
Hemorrhagic diathesis II
(Coagulation disorders)

2. Bleeding disorders
 4 categories:
 Bleeding disorders due to vascular abnormalities
 Bleeding disorders due to platelet abnormalities
 Disorders of coagulation factors
 Combination of all of the above (Disseminated
Intravascular Coagulation / DIC)

5. Coagulation disorders
 Factor VIII – hemophilia A
 Factor IX - Hemophilia B
 Christmas disease

6. Incidence
 X linked recessive
 1 in 5000 males
 Approx. 80% have factor VIII deficieny
 20% have factor IX deficiency
 In approx. 30%, no positive family history of the
disease - ? Genetic mutation.

7.  Factor VIII deficiency
 Factor VIII (antihemophilic factor) : protein that
circulates in the plasma and functions in the intrinsic
pathway of fibrin formation.
 Factor IX deficiency
 Factor IX – vitamin K dependent serine protease
that functions in the intrinsic pathway of fibrin
formation
.

8. Clinical symptoms
 Hemarthrosis, esp. in the knee – most common
feature of severe hemophilia.
 Subcutaneous hematomas – begin with slight
trauma and spread to involve a large mass of
tissue.
 Intramuscular hemorrhages – may result in
contracture and deformity

9.  Prolonged bleeding
 Primary hemostasis adequate to stop bleeding from
a minor cut, but because of deficient fibrin
stabilization, the platelet plug is dislodged –
bleeding begins a second time.
 Hematomas around tongue and throat
 Hemorrhages from the nose, mouth, gums
and other mucous membranes
 Others : hematuria and excess bleeding from
dental extractions

10. Laboratory aspects
 Laboratory screening tests –
 Prolonged APTT
 Platelet count – normal
 Bleeding time – normal
 PT – normal
 Definitive diagnosis –
 Specific factor assay

11. Therapy
Factor VIII deficiency
 Cryoprecipitate :
 prepared by freezing a unit of plasma and collecting
the precipitate that forms on thawing.
 Contains factor VIII, factor XIII, fibrinogen and von
Willebrand factor
 Factor VIII concentrate
 Deamino-D-arginine vasopressin (DDAVP)

12.  Factor IX deficiency :
 Treated with plasma or with concentrates that also
contain factors II, VII, and X (prothrombin complex
concentrates)

13. Disseminated Intravascular
Coagulation (DIC)
• DIC is an acute, subacute, or chronic
thrombohemorrhagic disorder characterized
by the excessive activation of coagulation,
which leads to the formation of thrombi in the
microvasculature of the body.
• It occurs as a secondary complication of many
different disorders.

14. • Sometimes the coagulopathy is localized to a
specific organ or tissue.
• As a consequence of the thrombotic diathesis
there is consumption of platelets, fibrin, and
coagulation factors and, secondarily,
activation of fibrinolysis.

15. Conditions Associated With DIC
• Infectious/Septicemia
– Bacterial
• Gm - / Gm +
– Viral
• CMV
• Varicella
• Hepatitis
– Fungal
• Intravascular
hemolysis
• Acute Liver Disease
• Tissue Injury
– trauma
– extensive surgery
– tissue necrosis
– head trauma
• Obstetric
– Amniotic fluid emboli
– Placental abruption
– Eclampsia
– Missed abortion

16. Conditions Associated With DIC
• Malignancy
– Leukemia
– Metastatic disease
• Cardiovascular
– Post cardiac arrest
– Acute MI
– Prosthetic devices
• Hypothermia/Hyperthe
rmia
• Pulmonary
– ARDS/RDS
– Pulmonary embolism
• Severe acidosis
• Severe anoxia
• Collagen vascular
disease
• Anaphylaxis

17. Pathogenesis
• Activation of coagulation: by release of tissue
factor
• Thrombotic phase: platelet adhesion and
aggregation with formation of thrombi and
emboli throughout the microvasculature
• Consumption phase: consumption of coagulation
factors and platelets
• Secondary fibrinolysis: causes breakdown of
fibrin resulting in fibrin degradation products in
circulation

18. Pathophysiology of disseminated
intravascular coagulation

19. Clinical Manifestations of DIC
ORGAN ISCHEMIC HEMOR.
Skin Gangrene
Acral cyanosis
Petechiae
Echymosis
Oozing
CNS Delirium/Coma
Infarcts
Intracranial
bleeding
Renal Oliguria/Azotemia
Cortical Necrosis
Hematuria
Cardiovascular Myocardial
Dysfxn
Pulmonary Dyspnea/Hypoxia
Infarct
Hemorrhagic
lung
GI
Endocrine
Ulcers, Infarcts
Adrenal infarcts
Massive
hemorrhage.

20. Clinical Manifestations of DIC

21. Microscopic findings in DIC
• Fragmented RBCs
• Paucity of platelets

22. Laboratory diagnosis
• Thrombocytopenia
– platelet count <100,000 or rapidly declining
• Prolonged clotting times (PT, APTT)
• Presence of Fibrin degradation products or
positive D-dimer

23. Treatment
• Prompt treatment of primary disease.
• Heparin therapy.
• Platelet transfusions.
• Replacement therapy with coagulation factors.

24. Thank you