Disorders of Secondary Hemostasis

What are four causes of plasma clotting factor issues?

1. Decreased synthesis

2. Production of abnormal molecules

3. Loss or consumption

4. Inactivation by antibodies or inhibitors

What are five symptoms of inherited disorders of plasma clotting factors?

1. Deep tissue bleeding

2. Moderate to severe bleeding of mucous membranes

3. Ecchymoses (NOT petechiae)

4. Spontaneous

5. Life threatening bleeds (trauma/surgery)

Inherited disorders affect how many factors?

Single factors

When is the onset of inherited disorders?

Evident from birth

What are the most common factors affected in inherited disorders?

1. Factor VIII

2. Factor IX

What are three causes of inherited factor disorders?

1. Factor decrease

2. Factor absence

3. Abnormal form

How do you determine whether its a qualitative or quantitative defect if the PT and/or APTT is prolonged?

1. Functional (clot-based) tests

2. Immunoassays

If the immunoassay is positive, what kind of defect is it? If the immunoassay is negative, what kind of defect is it?

1. Positive: Qualitative

2. Negative: Quantitative

What is the inheritance pattern for von Willebrand Disease?

Autosomal dominant or recessive

vWF is a carrier for what factor?

Factor VIII

Does Factor VIII vary with vWF?

Yes

How severe are the symptoms in von Willebrand’s disease?

Usually mild symptoms

von Willebrand’s disease is what kind of disorder and why?

Disorder of primary hemostasis since platelets can’t bind

What are two treatment options for von Willebrand’s disease?

1. Desmopressin Acetate

2. Factor VIII from human plasma

What is the expected bleeding time, platelet count, PT, APTT, PFA-100 and platelet aggregation results for vWD?

1. Prolonged bleeding time

2. Normal platelet count

3. PT normal

4. APTT prolonged

5. PFA-100: both closure times increased

6. No aggregation

What three tests make up the standard panel for vWD screening?

1. vWF: Antigenic properties of vWF protein

2. vWF: Rco: Functional Assay

3. FVIII: C: Functional activity of FVIII

How is the antigen vWF test measured? Is it qualitative or quantitative?

1. Measured by monoclonal antibodies with immunologic procedures

2. Quantitative

How is the functional assay measured, and is it quantitative or qualitative?

1. Measured by ristocetin cofactor activity

2. Qualitative

How is the FVIII functional assay measured and is it quantitative or qualitative?

1. Measured by APTT as a procoagulant in fibrin formation.

2. Qualitative

How many times is the panel performed?

2-3 times

What is the inheritance pattern for Hemophilia A?

X-linked recessive disorders

What percentage of Hemophilia A cases are the result of spontaneous mutation?

30%

What is the most common form of Hemophilia A?

Factor VIII:C

Which gender is more susceptible to Hemophilia A?

Male

What are four symptoms of Hemophilia A?

1. GI

2. Renal bleeds

3. Hemarthroses

4. Intracranial bleeds

The severity of symptoms in Hemophilia A correlates with what?

The concentration of FVIII

What concentration of FVIII corresponds to severe symptoms?

< 1% or 0-2 U/dL

What concentration of FVIII correlates to moderate symptoms?

2-5% or 2-6 U/dL

What concentration of FVIII correlates to mild hemophilia?

5-25% or 6-30 U/dL

What are two treatment options for Hemophilia A?

1. Halt bleeding

2. Prophylaxis

How can bleeding be stopped in Hemophilia A?

1. Raise level VIII:C with component therapy

2. Purified plasma products or synthetic

3. Drugs such as DDAVP

How often do patients with Hemophilia receive prophylaxis? What happens if they don’t get prophylaxis?

1. Once a week

2. They develop arthropathy

How many hemophiliacs have access to treatment?

30%

What is a problem with treatment?

They develop antibodies to missing factor

How many patients develop antibodies to FVIII? How many develop antibodies to FIX?

1. FVIII: 25%

2. FIX: 2-3%

What is the expected APTT, PT, platelet count, functional test, and Factor VIII:C results for Hemophilia A?

1. Prolonged APTT

2. Normal PT

3. Normal platelet count

4. Normal functional tests

5. Decreased Factor VIII:C

Which is more common: Hemophilia A or vWD?

vWD

How do you differentiate between Hemophilia A and vWF?

vWF has decreased vWF and VIII whereas Hemophilia A has decreased VIII only

Which has more severe bleeding: Hemophilia A or vWD?

Hemophilia A

Which disease only affects males: Hemophilia A or vWD?

Hemophilia A

Which has a prolonged BT: Hemophilia A or vWD?

vWD

Which disease has a prolonged PFA-100: Hemophilia A or vWD?

vWD

Which disease has a prolonged APTT: Hemophilia A or vWD?

Hemophilia A

Hemophilia B has a deficiency in what factor?

Factor IX

What is the inheritance pattern for Factor IX?

X-linked recessive

What are two lab results that correspond to Factor IX deficiency?

1. Abnormal APTT

2. IX decreased

What are the symptoms for Factor IX deficiency?

Same as Hemophilia A

What is the treatment for Hemophilia B?

Raise level of FIX in blood

What is the inheritance pattern for rare factor deficiencies?

Autosomal recessive

What is another name for hemophilia C, and what factor is it deficient in?

1. Rosenthal’s disease

2. Factor XI

What is the name of the disease that is deficient in factor XII? What does it cause?

1. Hagemen trait

2. Thromboses

Which factor deficiency has a clot that dissolves in urea?

Factor XIII

What factor deficiencies are usually asymptomatic?

PK and HMWK

What disease would you suspect if the patient is female?

vWD

What disease would you suspect if the patient is male?

Hemophilia

What are three defects of fibrinogen?

1. Afibrinogenemia

2. Hypofibrinogenemia

3. Dysfibrinogenemia

What is the cutoff for hypofibrinogenemia?

< 100 mg/dL

What is the inheritance pattern for fibrinogenemia?

Inherited autosomal dominant

What are the expected test results for fibrin defects?

Increased PT, APTT, TCT

What other defect accompanies fibrin?

Platelet function

What are most cases of fibrinogen defects the result of?

Acquired

What is a fibrinogen defect caused by excess utilization?

DIC

What is a fibrin defect that’s due to impaired production?

Liver Disease

What organ produces most factors and regulators?

Liver

Four causes of liver disease?

1. Hepatitis

2. Cirrhosis

3. Cancer

4. Poisoning

What does the liver produce in the absence of vitamin K?

PIVKAs

What are the expected results for PT, APTT, BT, PFA-100, and platelet count in liver disease?

1. Increased PT and APTT

2. BT increased

3. PFA-100 increased

4. Platelet count decreased

Why is the platelet count decreased?

1. hypersplenism

2. BM alcohol tox

3. Decreased thrombopoietin

4. Consumption (DIC)

What is the expected result of Thrombin Clotting Time, functional tests, and FDPs in liver disease?

1. TCT increased

2. Functional tests abnormal

3. FDPs increased

What are two ways to treat bleeding that occurs as a result of liver disease?

1. Component replacement

2. Antifibrinolytic therapy

What two blood blank products are given in the case of liver disease?

1. Fresh frozen plasma

2. RBCs

What drug is used for antifibrinolytic therapy?

Aminocaproic acid

What are four other acquired disorders?

1. Vitamin K deficiency

2. Renal failure

3. Acquired hemophilia

4. Acquired von Willebrands

how does renal failure affect hemostasis?

Affects level of coag factors and anticoagulants

How does acquired hemophilia affect hemostasis?

Development of autoantibodies to factors

How does Acquired von Willebrands affect hemostasis?

dysfunctional vWF

What are three forms of acquired circulating coagulants?

1. FDPs

2. Malignant paraproteins

3. Lupus anticoagulants

What are FDPs the result of?

1. DIC

2. Primary fibrinolysis

What percentage of hemophiliacs have inhibitors for factors?

8-10%

What are two forms of an acquired bleeding disorder?

1. Specific antibodies

2. Reversible protein/protein complexes

What are six causes of DIC?

1. Burns/trauma

2. Malignancies

3. Infections

4. Liver Disease

5. Obstetrical complications

6. Snake venoms

What does DIC do?

Triggers thrombin formation via TF pathway

What is the hallmark of DIC?

Circulating thrombin and plasmin

What are five aspects of DIC?

1. Simultaneous bleeding and thrombosis

2. Bleeding from at least 3 sites

3. Organ damage

4. Fever

5. Hypotension

What is the treatment for DIC?

1. Heparin

2. Treat underlying cause

What is the mortality rate for DIC?

54-87%

What are four causes of bleeding in DIC?

1. Consumption of coag factors

2. Degradation of coag factors by plasmin

3. Consumption of platelets

4. Interference by FDPs

What are four tests used to screen for DIC?

1. PT

2. APTT

3. Fibrinogen

4. D-dimer

What tests are included in the extended DIC profile?

1. TCT

2. Quantitative D-dimer

3. Antithrombin activity

4. Alpha-2 plasmin inhibitor level

What are five lab results for DIC?

1. Abnormal PT and APTT

2. D-dimer increased

3. FDP increased

4. Fibrinogen decreased

5. AT decreased

What are notable smear factors in DIC?

1. Fragmented RBCs (schistocytes)

2. Hemolysis 9decreased H & H

3. Leukocytosis

4. Left shift