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

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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
• 3. Redistribution of platelets

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PLATELETS ABNORMAL

• Hereditary Platelet Function Defects
• defects in adhesion, aggregation, secretion.
• Acquired Platelet Function Defects
• Drugs
• Uremia
• Liver disease
• Hematological disorders (e.g. leukemia)
• Infections (e.g. septicemia, HIV)

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Severe thrombocytopenia with petechial hemorrhages
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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. Splenic 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. Splenic 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 ABNORMALITIES

• Decreased Coagulation Bleeding
• Abnormal or decreased platelets
• Abnormal or decreased coagulation proteins
• Increased Coagulation Thrombosis
• Abnormal or increased platelets
• Increased coagulation proteins/decreased
  inhibitors of coagulation

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COAGULATION ABNORMALITIESBLEEDING

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

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COAGULATION ABNORMALITIES BLEEDING

• HEMOPHILIAS
• Sex linked genetic disorders
• Hemophilia A deficiency of factor VIII 1/1000
• Hemophilia B deficiency of factor IX 1/100,000
• Clinically
• severity levels of factors
• muscle hematomas and intra-articular bleeds
• post surgical and traumatic bleeds
• Therapy
• Factor concentrates, FFP, DDAVP

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HEMARTHROSIS
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COAGULATION ABNORMALITIES BLEEDING

• VON WILLEBRANDS DISEASE
• vWF has two important functions
• carries and stabilizes factor VIII
• platelet adherence in primary hemostasis
• Autosomal dominant deficiency of vWF
• Incidence 1/100- 1/3000
• Clinically presents like a platelet or vascular
  defect
• mucus membrane bleeding
• no intraarticular bleeds

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COAGULATION ABNORMALITIESBLEEDING

• 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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VIRCHOWs TRIAD
COAGULATION ABNORMALITIES THROMBOSIS
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COAGULATION ABNORMALITIESHYPERCOAGULABILITY/THROM
BOSIS

• Post operative state
• Malignancy
• Immobilization
• Pregnancy/ Estrogen use
• Previous venous thromboembolism
• Hereditary hypercoagulable states
• Factor V Leiden
• Prothrombin G20210A mutation
• Antithrombin deficiency
• Protein S/Protein C deficiency

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COAGULATION ABNORMALITIESDEEP VENOUS THROMBOSIS

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

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COAGULATION ABNORMALITIESDEEP VENOUS THROMBOSIS
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COAGULATION ABNORMALITIESTHROMBOSIS

• PREVENTION
• Decrease risk of stasis
• Counteract hypercoagulability
• 1. Antiplatelet drugs
• 2. Anticoagulants
• Heparin/Low Molecular Weight Heparin
• Coumadin
• Others
• 3. Fibrinolytics

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• 23-year-old female has had a bleeding problem all
  of her life (gum bleeding and heavy menstruation)
• A sister and an uncle have similar bleeding
  tendency
• Her platelet count is normal
• Her PT is normal and PTT is slightly prolonged
• The prolonged PTT is corrected (becomes normal)
  by 11 mixing with normal plasma
• Her factor VIII activity is 30 (N 50-150)
• Q. The most likely diagnosis for her bleeding
  tendency is
• A. Hemophilia A
• B. Von Willebrands disease
• C. Protein C deficiency
• D. Prothrombin G20210A mutation

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• 23-year-old female has had a bleeding problem all
  of her life (gum bleeding and heavy menstruation)
• A sister and an uncle have similar bleeding
  tendency
• Her platelet count is normal
• Her PT is normal and PTT is slightly prolonged
• The prolonged PTT is corrected (becomes normal)
  by 11 mixing with normal plasma
• Her factor VIII activity is 30 (N 50-150)
• Q. The most likely diagnosis for her bleeding
  tendency is
• A. Hemophilia A
• B. Von Willebrands disease
• C. Protein C deficiency
• D. Prothrombin G20210A mutation

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Disseminated Intravascular Coagulation Syndrome
Activation of clotting mechanism
Thrombosis
Fibrinogen- Fibrin Breakdown Products
Clot lysis
Consumption of platelets
Hemorrhage
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What did we learn today?

• Normal hemostasis
• List the common clinically significant
  disturbances of hemostasis
• Bleeding
• Thrombosis