Module 11.2 - Coagulopathies

Question 1

What is purpura?

Answer 1

• Diffuse hemorrhage into skin tissues that is visible through the skin causes a red-purple discoloration identified as purpura.
• Purpuric disorders occur when there are not enough platelets to plug damaged vessels or prevent leakage from minute tears that occur daily in normal capillaries

Question 2

What is thrombocytopenia?

Answer 2

Defined as a platelet count less than 150,000 platelets/mm3

Question 3

When can spontaneous bleeding occur?

Answer 3

Spontaneous bleeding without trauma can occur with counts between 10,000-15,000 platelets/mm3 and resulting in:

• Petechiae
• Ecchymosis
• Larger purpuric spots
• Frank bleeding from mucous membranes

Severe spontaneous bleeding may result if the count is < 10,000 platelets/mm3 resulting in perhaps fatal bleeding in the:

• GI system
• Respiratory system
• CNS system

Question 4

Describe the pathophysiology of thrombocytopenia

Answer 4

• Thrombocytopenia results from decreased platelet production increased consumption or both
• Can be congenital or acquired and primary or secondary to other conditions.

Question 5

What is and what causes acquired thrombocytopenia?

Answer 5

It is the most COMMON type of thrombocytopenia and occurs as a result of:

• Decreased platelet production secondary to:
• Viral infections (EBV, Rubella, CMV, HIV),
• Drugs (thiazides, ethanol, estrogens),
• Nutritional deficiencies (Vitamin B12 or folic acid in particular)
• Chronic renal failure
• Bone marrow hypoplasia (in aplastic anemia)
• Radiation therapy
• Bone marrow infiltration by cancer

Increased platelet consumption secondary to:

• Heparin induced thrombocytopenia (HIT)
• Idiopathic (immune) thrombocytopenic purpura (ITP)
• Thrombotic thrombocytopenic purpura (TTP) – uncommon and not discussed in this course

Question 6

What is and what causes Heparin-Induced Thrombocytopenia (HIT)?

Answer 6

• Heparin is a common drug induced thrombocytopenia
  
  • Approx. 4% of patients treated with unfractionated heparin develop HIT
• Incidence is lower with the use of lower molecular weight heparin
• Pathophysiology: HIT is an immune-mediated adverse drug reaction caused by IgG antibodies against the heparin-platelet factor 4 complex
• The release of additional platelet factor 4 from activated platelets and activation of thrombin lead to increased platelet consumption and a decrease in platelet counts beginning 5-10 days after administration of heparin.

Question 7

What are the clinical manifestations of Heparin-Induced Thrombocytopenia (HIT)?

Answer 7

• HALLMARK Clinical Manifestation: a reduction of approx. 50% in the platelet count is seen in more than 95% of affected patients.
• Bleeding is uncommon in those with HIT
• 30% of patients with HIT are at risk for venous or arterial thrombosis due to intravascular aggregation of platelets.
• Diagnosis: Based on clinical observations and a decrease in platelet count

Question 8

How do you treat Heparin-Induced Thrombocytopenia (HIT)?

Answer 8

• The withdrawal of heparin is the initial first treatment!
• Changing to low molecular weight heparin is not indicated and warfarin should not be used until the symptoms of HIT have resolved.
• The chance of spontaneous blood clots can be diminished using thrombin inhibitors (i.e. lepirudin and argatroban).

Question 9

What is Idiopathic (Immune) Thrombocytopenic Purpura (ITP)?

Answer 9

• MOST COMMON cause of thrombocytopenia secondary to increased platelet destruction
• Recognized now as an immune process
• ITP may be acute or chronic
• Acute form more common in children and may lead to chronic form

Question 10

What is CHRONIC Idiopathic (Immune) Thrombocytopenic Purpura (ITP)?

Answer 10

• Chronic ITP associated with autoantibodies against platelet specific antigens
• Most common in adults
• Highest prevalence in women between 20-40 years of age
• Tends to get progressively worse

Question 11

Describe the pathophysiology of Idiopathic (Immune) Thrombocytopenic Purpura (ITP)

Answer 11

Autoantibodies are generally of the IgG class (although IgA and IgM antibodies have been identified). They react against one or more of several platelet glycoproteins. The antibody-coated platelets are removed from the circulation by mononuclear phagocytes in the spleen.

Question 12

What are the clinical manifestations associated with Idiopathic (Immune) Thrombocytopenic Purpura (ITP)?

Answer 12

usually minor bleeding problems (development of petechiae and purpura) that occur over the course of several days and progress to major hemorrhage from mucosal sites (epistaxis, hematuria, menorrhagia, bleeding gums)

Question 13

How do you diagnose a patient with Idiopathic (Immune) Thrombocytopenic Purpura (ITP)?

Answer 13

Diagnosis of ITP is based on history of bleeding and associated symptoms such as weight loss, fever and headache

• PE includes notations on types of bleeding, location and severity
• Assessment includes history of infections (bacteria, HIV or other viruses)
• Obtain medication history and family history
• Evidence of thrombosis should be obtained

Diagnostic tests:

• CBC
• Peripheral blood smear

Question 14

How do you treat patients with Idiopathic (Immune) Thrombocytopenic Purpura (ITP)?

Answer 14

• Acute form usually resolves without major clinical consequences
• Chronic form course is variable with multiple remissions and exacerbations
• Treatment is initiated when platelet counts are < 30,000/mm3 or < 50,000mm3 with evidence of bleeding from mucous membranes.
• Treatment is palliative, not curative- focusing on prevention of platelet destruction
  
  • Initial therapy: Infusion of glucocorticoids (prednisone)- suppresses the production of antiplatelet antibodies and prevents sequestering and further destruction of platelets
  • If platelets do not response, treatment with IV immunoglobulin (IVIG) is used to prevent major bleeding
  • If all other therapies are ineffective, splenectomy is considered to remove the primary site of platelet destruction.

Question 15

What is Disseminated Intravascular Coagulation (DIC)?

Answer 15

• An acquired clinical syndrome characterized by widespread activation of coagulation resulting in formation of fibrin clots in medium and small vessels (microvasculature) throughout the body
• It is a secondary process concomitant with a pathophysiologic disease or clinical state.
• Disseminated clotting may lead to blockage of blood flow to organs, resulting in multiple organ dysfunction syndrome (MODS) leading to massive hemorrhage due to consumption of coagulation factors
• The magnitude of clotting may result in the consumption of platelets and clotting factors leading to severe bleeding
• The clinical course of DIC largely is determined by the intensity of the stimulus, host response and comorbidities, and it ranges from an acute, severe, life threatening process that is characterized by massive hemorrhage and thrombosis to a chronic low grade condition.
• The chronic condition is characterized by subacute hemorrhage and diffuse microcirculatory thrombosis.
• DIC may be localized to one specific organ or generalized, involving multiple organs.

Question 16

How do you diagnose a patient with Disseminated Intravascular Coagulation (DIC)?

Answer 16

• Because of the complexity and wide variations in manifestations of DIC, the diagnosis has been challenging.
• An abnormal stimulus results in the formation of excess thrombin, which, in turn, causes the following:
  
  1. Fibrinogen consumption
  2. Irreversible platelet aggregation
  3. Activation of the fibrinolytic system

Question 17

What are the risk factors for Disseminated Intravascular Coagulation (DIC)?

Answer 17

• Cancer
• Products of conception; preeclampsia, eclampsia, amniotic fluid embolism
• Severe toxic or immunologic reactions – snake bite, transfusion reaction, transplant rejection
• Sepsis is the MOST common condition associated with DIC due to damage to vascular endothelium
  
  • Gram negative microorganisms (gram – endotoxins are PRIMARY cause of endothelium damage and occurs in up to 50% of individuals with gram - sepsis),Fungi, Protozoa (malaria), and Viruses (influenza, herpes)
• DIC occurs in about 2/3 of individuals with a systemic inflammatory response to trauma
• Other causes included blood transfusion. Transfused blood dilutes the clotting factors, as well as circulating naturally occurring anti-thrombin.
• In hemolytic transfusion reactions, the endothelium is damaged by complement-mediated reactions.

Question 18

What are the clinical manifestations associated with Disseminated Intravascular Coagulation (DIC)?

Answer 18

Bleeding complications are the MOST COMMON

• The patient may exhibit mild symptoms, such as oozing from venipuncture sites or wounds
• Typically, bleeding occurs from multiple sites
• Development of petechiae, purpura, ecchymosis and hematomas

The patient may complain of bleeding that is:

• Oral
• Gingival
• Gastrointestinal
• Genitourinary

Acute DIC

• Tachycardia
• Hypotension
• Edema
• Jaundice- from red blood cell destruction

Other possible findings:

• Spontaneous bleeding
• Gastrointestinal bleeding
• Respiratory tract bleeding
• Hematuria
• Persistent bleeding at venipuncture sites or wounds
• Skin necrosis
• Venous thromboembolism

Thrombosis

• May be superficial or deep venous
• Digital ischemia and gangrene are the MOST COMMON forms
• Thrombosis is most common in patients with malignancy

Question 19

What laboratory tests are used to diagnose Disseminated Intravascular Coagulation (DIC)?

Answer 19

• NO singular laboratory test is diagnostic
• Of the fibrin degradation products, the D-Dimer is the MOST SENSITIVE
• HYPO-fibrinogenemia is also a very important finding as limited disorders cause this finding.

Consider ordering the following:

• Blood cultures to rule out sepsis
• Repeat fibrinogen levels and partial thromboplastin time (PTT)
• Diagnosis is confirmed by rapidly falling fibrinogen levels (fibrinogen half-life is approx.. 4 days)

Question 20

What are some laboratory findings associated with acute uncompensated Disseminated Intravascular Coagulation (DIC)?

Answer 20

• Elevated D-dimer
• Thrombocytopenia: platelet count < 150,000/microL
• Prothrombin time (PT) and aPTT are prolonged by 70% and 50% respectively
• Fibrinogen, factor V and factor VII levels are low
• Fragments RBCs (schistocytes) are found on the peripheral blood smear.

Question 21

What are some laboratory findings associated with chronic/compensated Disseminated Intravascular Coagulation (DIC)?

Answer 21

• Elevated fibrin degradation product levels (FDPs > 45 microg/mL)
• D-Dimer is MOST sensitive (positive at > 1:8 dilution) for differentiating DIC from primary fibrinolysis

Question 22

How do you manage patients with Disseminated Intravascular Coagulation (DIC)?

Answer 22

• Hematology consult for suspected cases
• Diagnose and correct underlying cause: PRIORITY in management
  
  • Correct hypotension
  • Control sepsis
  • Deliver placenta or stillborn fetus
• If hemorrhagic complications are significant, maintenance of blood volume and hemostatic function is warranted:
  
  • Packed RBCs
  • Replacement therapy by platelet transfusion with a GOAL: Platelet count between 30,000-50,000/microL
  • Cryoprecipitate:
    
    • GOAL: plasma fibrinogen level of 150mg/dL
    • One (1) unit of cryoprecipitate increases fibrinogen level by approximately 6-8 mg/dL
    • Administration of 15 units of cryoprecipitate raises the level from 50-150mg/dL
  • Fresh frozen plasma every 30 minutes in severe DIC.
• Supportive therapy includes treating hypoxemia and any hemodynamic compromise
• Heparin therapy is controversial
• Temperature has an effect on coagulation factor enzymes. Literature suggests that for each decrease of 1 degree Celsius, it will reduce activities of coagulation factor enzymes by approx. 10%.