Bleeding, Thrombotic and Fibrinolytic Disorders

Question 1

Immune Thrombocytopenia (ITP)

Answer 1

Etiology: Usually idiopathic

Can be secondary
Autoimmune disorders lupus and others
Medications (sulfonamides, thiazides, cimetidine, Heparin)
Viral infections such as HIV, Hepatitis C
In children can often be provoked by a viral illness

Question 2

Thrombotic thrombocytopenia purpura (TTP)

Answer 2

Antibodies against ADAMTS-13 which is responsible for cleaving large vWF molecules into smaller pieces

Extensive platelet aggregation and fibrin bridging

Shear force on RBCs lead to destruction

Question 3

Hemolytic uremic syndrome (HUS)

Answer 3

caused by endothelial damage secondary to bacterial toxins.

is secondary to E. coli 0157:H7 but may be caused by others.

Question 4

Immune Thrombocytopenia (ITP) MOA

Answer 4

Antibodies bind platelets
Leads to destruction of platelets
Inadequate production of platelets

Question 5

Clinical manifestations of ITP

Answer 5

Mucocutaneous bleeding (blood blisters in mouth)
Petechiae, purpura
Spontaneous bruising
Nosebleeds
gingival bleeding
Retinal hemorrhage
Excessive menstrual bleeding
Melena, hematuria

Question 6

Making the diagnosis of ITP includes

Answer 6

Thrombocytopenia
Normal RBC morphology
Prolonged bleeding time
\+/- anemia
PT/PTT are normal
Bone marrow biopsy
Normal or increased number of megakaryocytes

Question 7

Treatment of ITP

Answer 7

Treat if platelet counts are less then 20-30,000 or if significant bleeding

Oral steroids with prednisone or dexamethasone

May give platelet transfusion if needed

Question 8

There are 5 main characteristics of TTP

Answer 8

Thrombocytopenia
Microangiopathic hemolytic anemia
Neurologic symptoms
Kidney failure (may be mild or absent)
Fever (75% of patients)

Question 9

Organ damage from TTP

Answer 9

occurs primarily in the kidneys and brain.

Microscopic clotting leads to end organ damage due to ischemia

Question 10

TTP Symptoms

Answer 10

Malaise
Diarrhea
Thrombocytopenia = bruising, bleeding
Microvascular clotting leads to organ damage = kidney failure, neurologic symptoms and others

Question 11

Laboratory abnormalities seen in TTP

Answer 11

Microangiopathic hemolytic anemia (prominent rbc fragmentation)

Elevated indirect bilirubin

Decreased serum haptoglobin

Severely elevated LDH (lactate dehydrogenase)

Question 12

Treatment of thrombocytopenic purpura

Answer 12

Main treatment is plasma exchange

Early diagnosis and treatment is essential

Without treatment 90% of patients die

Question 13

HUS causes Endothelial damage (NOT seen in TTP) and inappropriate platelet aggregation lead to significant morbidity from

Answer 13

Microangiopathic hemolytic anemia

Acute kidney injury and renal failure

Thrombocytopenia

Question 14

Signs and symptoms of hemolytic uremic syndrome.

Answer 14

Recent or current bloody diarrhea
Abdominal pain
Decreased urine output
Hematuria
Renal failure
Hypertension
Neurologic changes
Edema

Question 15

General management of HUS

Answer 15

Supportive Management:
Transfuse RBCs and platelets if needed
Dialysis if symptomatic uremia
Nutritional and electrolyte support
If thought to be secondary to an autoimmune process may consider plasma exchange

Question 16

Henoch-Schönelin purpura (HSP)

Answer 16

IgA vasculitis
90% of cases occur in children 3-15 years old
Can be triggered by a streptococcal upper respiratory infection
Should not have associated thrombocytopenia or coagulopathy

Question 17

Four major symptoms are associated with HSP

Answer 17

Palpable purpura
Arthritis/arthralgias
Abdominal pain
Renal disease

Question 18

HSP Treatment

Answer 18

Treatment is supportive with NSAIDs or glucocorticoids

Renal failure from IgA deposition may not be evident for 6 months so follow up is necessary

Work up includes biopsy of the skin lesions, CBC, comprehensive metabolic panel, urinalysis (may show hematuria, +/- rbc casts, +/- proteinuria)

Question 19

Hemophilia

Answer 19

Incidence: 1/5000
X linked recessive (predominantly males)
Females – carriers (can have some degree of deficiency)

Question 20

Hemophilia Types

Answer 20

Hemophilia A = Factor VIII deficiency
80% of patients
2/3 have severe disease

Hemophilia B = Factor IX deficiency
Also known as Christmas disease

Hemophilia C = Factor XI deficiency
Rare
1/1,000,000

Question 21

Bleeding in hemophilia

Answer 21

Characteristic of this disease is spontaneous hemarthrosis (bleeding in a joint)
At risk for spontaneous intracerebral hemorrhage
Most common bleeding sites:
Joints: knees, ankles, elbows
Skin, muscle
GU, GI

Question 22

Treatment for hemophilia

Answer 22

Replace the deficient factor usually 3 times per week: IV bolus for home administration
Extra dose given if needed due to trauma or suspicion of joint bleeding
Avoid aspirin
Cryoprecipitate
DDAVP

Question 23

von Willebrand Disease

Answer 23

Autosomal dominant affecting both sexes equally

Most common inherited bleeding disorder

Question 24

2 main functions of von Willebrand factor

Answer 24

Binds platelets to form the initial platelet plug

Binds with Factor VIII to prolong it’s half life

Question 25

Three distinct types of von Willebrand disease

Answer 25

``` Type 1 (75-80% of patients) Quantitative abnormality of vWF Type 2 (several variants) Qualitative abnormality Decreased binding to factor VIII and platelets Clinically resembles hemophilia A Type 3 (rare) Undetectable levels of vWF and severe bleeding in infancy and childhood ```

Question 26

von Willebrand disease Symptoms

Answer 26

Symptoms can occur at any age | Easy bruising, skin bleeding, prolonged bleeding from mucosal surfaces

Question 27

Disseminated Intravascular Coagulation (DIC)

Answer 27

Massive release of tissue factor Tissue factor then sets the coagulation system in place Coagulation occurs Clotting factors and inhibitors are consumed Clots further trap circulating platelets leading to ischemia

Question 28

DIC Manifestations

Answer 28

Thrombosis and hemorrhage Petechia, purpura, gangrene Renal failure, liver failure In cancer patients it can be of slow onset

Question 29

DIC Labs

Answer 29

``` Thrombocytopenia Prolongation of PT and PTT Low fibrinogen Increased levels of fibrinogen degradation products (d-Dimer) Schistocytes (helmet cells) ```

Question 30

Protein C Deficiency

Answer 30

important regulating component of the clotting cascade inactivates Factors V and VIII thereby inhibiting anticoagulation A deficiency of Protein C leads to prolonged action of Factors V and VIII leading to excessive clotting No signs or symptoms are recognized until clots form.

Question 31

Protein S Deficiency

Answer 31

supports the function of Protein C. needed for proper function of Protein C. A deficiency in Protein S results in diminished ability of Protein C to inactivate Factors V and VIII resulting in excessive clotting

Question 32

Antithrombin III Deficiency

Answer 32

Usually autosomal dominant Recurrent venous thrombosis, pulmonary embolism and repetitive intrauterine fetal death About 60% of patients that are deficient have recurrent thrombotic episodes Peak age at onset is 15-35 years old

Question 33

Factor V Leiden

Answer 33

Most common genetic disorder to cause DVT. 5% of the general population Blood has an increased tendency to clot and is most likely to occur in the veins Lack of Factor V Leiden decreases the anticoagulant activity of the activated protein C

Question 34

Antiphospholipid antibody

Answer 34

Clotting disorder secondary to autoimmune process. Autoimmune hypercoagulable state caused by antiphospholipid antibodies Antibodies lead to arterial and venous clot formation Pregnancy complications: miscarriage, stillbirth, preterm delivery, severe eclampsia End organ damage