Bleeding & Clotting Disorders
By
Dr. Sumaira Iqbal
LEARNING OBJECTIVES
• By the end of lecture student should be able to
• Comment on physiological basis of bleeding, platelet and coagulation disorder including hemophilia and thromoboembolic diseases
• Relate Coagulation profile with disorders
Bleeding disorders
• Vessel wall disorder
• Platelet disorder
• Congenital coagulation disorders
– Hemophilia A
– Hemophilia B
– Von Willibrand’s Disease
VESSEL WALL DISORDER
SCURVY• Vitamin C Deficiency
• Vit C level falls below 10mg/d
• Essential for synthesis of collagen.
• Hemorrhage in muscles , joints , nail beds & gingival tissues.
VESSEL WALL DISORDER
• GINGIVITIS PRESENTATION– Swelling
– Friability
– Bleeding
– Secondary infection
– Loosening of teeth
• Treatment:– Diet rich in Vitamin C
– Administration of 1g/d of Vitamin C supplements
PLATELET DISORDERS
• CONGENITAL
• ACQUIRED
THROMBOCYTOPENIA
• Quantity of platelets when reduced by
– Decreased production in the bone marrow
– Increased sequestration in the spleen
– Accelerated destruction
TREATMENT: Platelet Transfusion.
PLATELET DISORDERS
THROMBOCYTOPENIA
Causes:
• Drug induced like ASPIRIN
• Bone marrow failure
• Hypersplenism
• Idiopathic
• Lymphomas
• Aplastic anemia
PLATELET DISORDERS
THROMBOCYTOPATHIES
Qualitative defects in platelet ADHESION, AGGREGATION, RELEASE OF COAGULATION FACTORS,
Conditions like
Glanzman’s Thrombasthenia
Bernard soulier syndrome
PRESENTATION
• Skin purpura
• Superficial bruising
• Epistaxis
• Menorrhagia
• Mucosal hemorrhage is seen in severe cases and intra-cranial hemorrhage is rare.
IDIOPATHIC THROMBOCYTOPENIA• Caused by accelerated antibody mediated platelet
destruction
• CAUSE: not known
• Oral hematomas & hemorrhagic bullae may occur
• Intracanial hemorrhage is the most common cause of death
• TREATMENT
– Blood transfusion
– Splenectomy
– Corticosteroids
COAGULATION DISORDER
• Disorders of formation and activation
• Decreased formation --- Liver diseases like
– Cirrhosis of liver
– Hepatitis
– Yellow atrophy
• Vitamin K deficiency
– Activates II, VII, IX, X and protein C
COAGULATION DISORDER
• Vit-K ----- liver carboxylase
– Add carboxyl group to glutamic acid residue
– Vitamin K becomes oxidized and inactive
– Vitamin K epoxide reductase bring back it to reduced and active form
• Synthesized in intestines
• Deficiency is rare in adults
• Deficiency results from poor absorption of fats
• May occur due to inappropriate bile secretion
HEMOPHILIA
• Deficiency of Factor VIII (Antihaemophilic factor)
• Also known as classic hemophilia
• Inherited as an X – linked trait.
• 10 times more commonly than hemophilia–B
• In 85% cases hemophilia is due to deficiency of factor VIII
• In 15% cases hemophilia is due to deficiency of factor IX
HEMOPHILIA
CLINICAL FEATURES
• No racial predilection• AGE-Bleeding manifestations begin after 6
months of age• SIGNS:
– Hematomas,– Hemarthroses– Hematuria– GI bleeding– Bleeding from laceration– Spontaneous intra cranial bleeding
HEMOPHILIA
• TREATMENT
– Factor VIII concentrates
VON WILLEBRAND’S DISEASE
• Deficiency of VWF & amount of Factor VIII
• Von Willebrand factor
– Synthesis in endothelium and megakaryocytes
– Smaller component of factor VIII
– Anchors platelets to subendothelium
– Bridge between platelets
• Inheritance - autosomal dominant
• Incidence - 1/10,000
• Clinical features – similar to hemophilia
CHRISTMAS DISEASE
• Hereditary deficiency of factor IX.
• Inherited as X – linked recessive trait
• Very rare compared to Hemophilia-A
• Clinical presentation same as Hemophilia A
• TREATMENT:
Recombinant factor IX
THROMBOEMBOLIC CONDITIONS
THROMBOEMBOLIC CONDITIONS
• THROMBOSIS
“Pathological formation of hemostatic plug within the vasculature (in vivo) in the absence of bleeding”
• EMBOLUS
“Detachment of clot from the actual site and flow freely in blood”
THROMBOEMBOLIC CONDITIONS
• Thromboembolic conditions
• Conditions favour thrombus formation
– Rough endothelial surface
(Atherosclerosis, infection or trauma)
– Sluggish blood flow
(Polycythemia or CHF)
• Disseminated intravascular coagulation
– Septicemia
• Emboli that originate from large arteries or in the left side of heart plug small arteries or arterioles of brain and kidneys.
• While emboli originate from venous system or right side of heart plug pulmonary arteries.
Disseminated Intravascular Coagulation
• Clotting mechanism is activated in widespread areas of circulation
• Presence of large amount of traumatized that release great quantity of tissue factor into blood
• Also seen in septicemia in which bacterial endotoxins activate clotting mechanism
• Plugging of small vessels leads to inefficient nutrient and oxygen provision
• Lack of blood flow
Systemic activation
of coagulation
Intravascular
deposition of fibrinDepletion of platelets
and coagulation factors
BleedingThrombosis of small
and midsize vessels
with organ failure
Disseminated Intravascular Coagulation
• Diagnosis
–FDPs raised
• Treatment
– Treatment of underlying disorder
– Anticoagulation with heparin
– Platelet transfusion
BLOOD COAGULATION TESTS
Coagulation profile
• Bleeding time
• Clotting time
• Prothrombin time
• INR
Bleeding Time (BT)
is the time interval between the skin puncture and spontaneous, unassisted (i.e. without pressure)
stoppage of bleeding. The BT test is an in vitro test of platelet function.
• 1-5 minutes
• Prolonged in thrombocytopenia (primary)
• Normal in clotting disorders
Clotting time (CT)
is the time interval between the entry of blood into the glass capillary tube, or a syringe, and
formation of fibrin threads
• 2 – 4 minutes
• Give the information of clotting factors
Prothrombin time
Measures the time required for fibrin clot to form when plasma is added to thromboplastin
and calcium in oxalated blood
• Normal = 12 seconds
• Prolonged in
– Deficiency of I, II, V, VII & IX
– Liver disease
– High dose heparin
INR
• International normalized ratio is determined to standardize PT
• (PTtest /PTnormal)ISI
• ISI : 1-2
• INR– Normal = 0.9—1.3
– High = 4– 5 (bleeding)
– Low = 0.5 (clot)
– Warfarin therapy = 2– 3
DisorderBleeding
TimePlatelet count
PT APTTFibrinogen
Assay
Thromboc-ytopenia
Prolonged Decrease Normal Normal Normal
Vit – K Deficiency
Normal Normal Prolonged Prolonged Normal
Qualitative Platelets Defects
Prolonged Normal Normal Normal Normal
Classic Hemophilia
Normal Normal Normal Prolonged Normal
Christmas Disease
Normal Normal Normal Prolonged Normal
Von Willebrand
DiseaseProlonged Normal Normal Prolonged Normal
DIC Prolonged Decrease Prolonged Prolonged Prolonged