DISORDERS OF PLATELETES

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DISORDERS OF PLATELETES
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Hemostasis

• Clotting after vascular injury consists of 2
  stages
• Primary hemostasis ? the job of the platelets
• A tempory fix, lasts 12-24 hrs
• Secondary hemostasis ? the job of the coagulation
  factors

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Primary HemostasisPlatelets

• Adhesion the deposition of platelets on the
  subendothelial matrix
• Secretion the release of platelet granule
  proteins
• Aggregation platelet-platelet cohesion
• Pro-coagulant activity the enhancement of
  thrombin generation

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Primary HemostasisPlatelets
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Primary HemostasisPlatelets

• Platelet Adhesion
• Endothelial injury
• Platelets rapidly attach to the subendothelial
  collagen GP1a-IIa
• Via von Willebrand Factor released from the
  endothelium
• vWF binds with the platelet surface glycoprotein
  Ib-IX
• Increases adherence of the platelets to each
  other and the exposed endothelium

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Primary HemostasisPlatelets

• Platelets Secretion
• ADP leads to surface expression of (ICAM)-1 on
  endothelial cells
• Platelets release arachidonic acid which is
  converted by cyclooxygenase to precursors of TXA2
• TXA2 is a potent stimulator of platelet
  aggregation and a potent vasoconstrictor
• ASA irreversibly binds cyclooxygenase thereby
  inhibiting platelet aggregation NSAIDs
  reversibly bind cyclooxygenase

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Primary HemostasisPlatelets

• Platelet Aggregation
• The same factors that stimulate release also
  stimulate aggregation
• Fibrinogen cross links platelets via the IIb-IIIa
  proteins
• GP IIb-IIIa ? Fibrinogen receptor
• GP IIb/IIIa inhibitors such as Aggrastat
  (tirofiban), Integrilin (eptifibamide) and Reopro
  (abciximab) work by blocking platelet aggregation

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Primary HemostasisPlatelet Abnormalities

• Superficial bleeding
• Mucosal
• Epistaxis
• Gingival bleed
• Buccal mucosa
• Skin
• Petechiae small capillary hemorrhage
• Ecchymoses small, superficial bleed
• Immediate bleeding

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Thrombocytopenia

• Symptoms / Signs
• Purpura purple colored skin manifestations
• Ecchymoses (bruising), petechiae
• Splenomegaly (sequestration)
• Usually no sx with platelets gt50K/ µL
• Concern when platelets lt30K/ µL especially with
  evidence of platelet dysfunction
• Cerebral hemorrhage usually only occurs with
  platelets lt10-15K/ µL

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Disorders of Primary Hemostasis

• Abnormal platelet function
• von Willebrand disease
• ASA use/ ingestion
• Bernard-Soulier syndrome
• Glanzmann thrombasthenia
• Abnormal platelet number (thrombocytopenia)
• Splenic sequestration (hypersplenism)
• Platelet survival defect (DIC, TTP, ITP, HELLP,
  drugs)
• Platelet production defect (BM failure)
• Dilutional, from massive fluid resuscitation

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Abnormal Platelet NumberThrombocytopenia

• Splenic sequestration (hypersplenism)
• Platelet survival defect
• ITP
• HUS-TTP
• Heparin
• Platelet production defect (BM failure)

• Dont forget to confirm low platelet count
• Repeat test
• Look at smear? clumping/ lab artifact?

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Thrombocytopenia

• ITP (Idiopathic Thrombocytopenic Purpura)
• Childhood Form- Acute
• High spontaneous remission rate (gt80)
• Strongly associated with parvovirus B19 infection
  
• Adult Form Chronic /- relapsing     
• 70 women 70 lt40 years old
• Antibodies to platelet glycoproteins
• Association with SLE and HIV
• Treat with steroids IVIG, Anti-D (WINRHO) if
  Rh, splenectomy if refractory

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Thrombocytopenia

• TTP (Thrombotic Thrombocytopenic Purpura)
• Pentad of
• Fever
• Anemia, Microangiopathic Hemolytic (Schistocytes)
• Thrombocytopenia
• Renal Abnormalities
• Neurological Abnormalities
• Two Types
• Congenital and Acquired
• LIFE THREATENING- 25 Mortality
• Treat with plasmapheresis

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Thrombocytopenia

• HUS (Hemolytic Uremic Syndrome)
• Similar to TTP except HUS mainly affects kidney
  vasculature.
• Similar hemolytic anemia, thrombocytopenia,
  purpura, and ARF but no CNS symptoms.
• Secondary to E. Coli 0157H7, others.
• Treatment with dialysis, plasmapheresis

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Thrombocytopenia

• Heparin-induced thrombocytopenia (HIT)
• Autoimmune antibodies to heparin and platelets
• Treat by discontinuing heparin
• White CLOT Syndrome (type 2 HIT)
• Complication with rapid decline of platelets with
  thrombus formation
• Arterial venous thromboses
• Must stop heparin
• Treat with lytics, or alternative heparin
  (hirudin)

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Abnormal Platelet Functionvon Willebrand Disease

• vWF deficiency
• Most Common inherited bleeding disorder (1)
• Mild symptoms in normal situations
• Increased bleeding with surgery or trauma
• Plt dysfunction is major sign
• nosebleeds
• gum bleeding
• petechiae
• /- menorrhagia or GI hemorrhage

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Abnormal Platelet Functionvon Willebrand Disease

• Classification of von Willebrand's Disease
• Type 1 (90) deficiency of vWF (mild) AD
• Type 2 nl levels, abnormal function AD
• Type 3 deficiency of vWF SEVERE rare AR
• Family history gives big clue!

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Abnormal Platelet FunctionOther Causes

• Drugs ASA/ NSAIDs
• Bind to cyclooxygenase
• Block synthesis of thromboxane A2
• Bernard-Soulier Syndrome
• No glycoprotein Ib? cannot bind vWF
• Very poor platelet adhesion
• Modestly low platelet count
• Glanzmanns thrombasthenia
• Deficient GP IIb-IIIa complex? poor aggregation
• Normal platelet count

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Abnormal Platelet FunctionOther Causes

• Uremia
• Causes prolonged bleeding time
• Treat with transfusions for active bleeding, or
  DDAVP pre surgery.
• Paraproteinemia
• Multiple myeloma or connective tissue diseases
• Coat platelets, intefere w/ function

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