Hemostasis

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Hemostasis Coagulation Abnormalities

• Dr. Imran Mirza
• Department of Laboratory Medicine Pathology
• University of Alberta

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Learning Objectives

• Describe normal hemostasis
• List the common clinically significant
  disturbances of hemostasis and describe their
  clinical features

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HEMOSTASIS

• Hemostasis is the interaction of platelets,
  vessels and clotting factors to stop bleeding.
• Hemostatic disorders can be either platelet or
  coagulation cascade problems.

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FACTORS CONCERNED WITH HEMOSTASIS

• Integrity of small blood vessels
• Adequate numbers of platelets
• Normal amounts of coagulation factors
• Normal amounts of coagulation inhibitors
• Adequate amounts of calcium ions in the blood

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MEGAKARYOCYTE TO PLATELETS

• Very large in size.
• Abundant pale staining cytoplasm with granules.
• Platelets are formed by fragmentation of
  cytoplasm.
• A bare nucleus remains.

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PLATELETS

• Smallest corpuscular component of blood but are
  not true cells!
• Cytoplasmic fragments of megakaryocytes
• Lifespan of 7-10 days

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PLATELETS AND HEMOSTASIS
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PRIMARY CLOTTING
Endothelium
vWF
Fibrinogen
GP Ib
Collagen
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REVIEW OF CLOTTING
Endothelial Damage 10 Clotting
Platelet Adhesion Activation
Aggregation 20 Clotting Coagulation Cascade
vWF Agonists Fibr
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PLATELETS INCREASED

• Thrombocytosis platelet count gt450 x 109/L
• Reactive Thrombocytosis
• Response to infection/inflammation, hemorrhage
• Post splenectomy
• Iron deficiency
• Malignancy e.g. Essential thrombocythemia (ET)
• Degree of elevation is useful in their
  separation
• gt1500 x 109/L is almost exclusively due to ET

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PLATELETS DECREASED

• Thrombocytopenia platelets lt150 x 109/L
• Risk of bleeding with thrombocytopenia
• if lt 50 - surgical or post traumatic bleeds
• if lt 15 - spontaneous bleeds
• Causes of thrombocytopenia
• 1. Failure of production
• 2. Increased platelet destruction
• usually due to autoantibodies spleen

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• 35-year-old female with heavy menstrual flow for
  the past 6 months
• Pinpoint hemorrhages on her legs in the past
  month.
• CBC shows normal HGB and WBCs, but ? platelets
• (19 x 109/L N150-450 x 109/L)
• On admission, she is given a transfusion of
  platelets, but counts do not improve.
• Splenectomy is performed with improvement in
  platelet counts.
• Q. The most likely basis for her bleeding
  tendency is
• A. Abnormality of platelet production by
  megakaryocytes
• B. Suppression of stem cells
• C. Excessive loss of platelets in menstrual
  blood
• D. Sequestration/destruction of platelets
• E. Defective platelet-endothelial interaction

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• 35-year-old female with heavy menstrual flow for
  the past 6 months
• Pinpoint hemorrhages on her legs in the past
  month.
• CBC shows normal HGB and WBCs, but ? platelets
• (19 x 109/L N150-450 x 109/L)
• On admission, she is given a transfusion of
  platelets, but counts do not improve.
• Splenectomy is performed with improvement in
  platelet counts.
• Q. The most likely basis for her bleeding
  tendency is
• A. Abnormality of platelet production by
  megakaryocytes
• B. Suppression of stem cells
• C. Excessive loss of platelets in menstrual
  blood
• D. Sequestration/destruction of platelets
• E. Defective platelet-endothelial interaction

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Intrinsic Pathway - PTT
Extrinsic Pathway PT/INR
12 11 9 8
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10 5 2 1
HEPARIN COUMADIN
CLOT
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COAGULATION CASCADE DEFECTS

• Hereditary
• A. Hemophilia A
• B. Hemophilia B
• C. Von-Willebrands Disease
• Acquired
• A. Vitamin K deficiency
• factors II, VII, IX, X
• B. Liver disease

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HEMOPHILIAS

• Sex linked genetic disorders
• Hemophilia A deficiency of factor VIII 1/1000
• Hemophilia B deficiency of factor IX 1/100,000
• Clinically
• severity is dependant on levels of factors
• muscle hematomas and intra-articular bleeds
• post surgical and traumatic bleeds can be life
  threatening
• Therapy
• Factor concentrates, FFP, Others

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HEMARTHROSIS
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VON WILLEBRANDS DISEASE

• vWF has two important functions
• carries and stabilizes factor VIII
• platelet adherence in primary hemostasis
• Autosomal dominant deficiency of vWF
• 1/100- 1/3000
• Clinically presents more like a platelet or
  vascular defect
• mucus membrane bleeding
• post surgical or traumatic bleeding
• no intra-articular bleeds

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BLEEDING DISORDERS

• Vascular/Platelet Defects Coagulation Defects
• Prolonged bleeding Prolonged bleeding
• Petechiae easy bruising Deep Hematomas
• Skin and mucus membranes Hemarthrosis
• Non-recurrent bleeding Recurrent bleeding

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HYPERCOAGULABLE STATES/THROMBOSIS

• VIRCHOWs TRIAD

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HYPERCOAGULABLE STATES/THROMBOSIS

• Post operative state
• Malignancy
• Immobilization
• Pregnancy/ Estrogen use
• Previous venous thromboembolism
• Hereditary hypercoagulable states
• Abnormal coagulation proteins
• Deficiency of anticoagulant proteins

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DEEP VENOUS THROMBOSIS

• Clinical features of DVT
• red
• warm
• swollen
• tender
• symptoms of a pulmonary embolus
• shortness of breath, hypoxia, pulmonary
  hypertension
• sudden death

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DEEP VENOUS THROMBOSIS
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PREVENTION OF THROMBOSIS

• A. Decrease risk of stasis
• B. Counteract hypercoagulability
• 1. Antiplatelet drugs
• 2. Anticoagulants
• Heparin
• Coumadin
• Others
• C. Thrombolysis
• Fibrinolytics

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Disseminated Intravascular Coagulation Syndrome
Activation of clotting mechanism
Thrombosis
Fibrinogen- Fibrin Breakdown Products
Clot lysis
Consumption of platelets
Hemorrhage