Bleeding, Thrombotic and Fibrinolytic Disorders Flashcards
Immune Thrombocytopenia (ITP)
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
Thrombotic thrombocytopenia purpura (TTP)
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
Hemolytic uremic syndrome (HUS)
caused by endothelial damage secondary to bacterial toxins.
is secondary to E. coli 0157:H7 but may be caused by others.
Immune Thrombocytopenia (ITP) MOA
Antibodies bind platelets
Leads to destruction of platelets
Inadequate production of platelets
Clinical manifestations of ITP
Mucocutaneous bleeding (blood blisters in mouth) Petechiae, purpura Spontaneous bruising Nosebleeds gingival bleeding Retinal hemorrhage Excessive menstrual bleeding Melena, hematuria
Making the diagnosis of ITP includes
Thrombocytopenia Normal RBC morphology Prolonged bleeding time \+/- anemia PT/PTT are normal Bone marrow biopsy Normal or increased number of megakaryocytes
Treatment of ITP
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
There are 5 main characteristics of TTP
Thrombocytopenia Microangiopathic hemolytic anemia Neurologic symptoms Kidney failure (may be mild or absent) Fever (75% of patients)
Organ damage from TTP
occurs primarily in the kidneys and brain.
Microscopic clotting leads to end organ damage due to ischemia
TTP Symptoms
Malaise
Diarrhea
Thrombocytopenia = bruising, bleeding
Microvascular clotting leads to organ damage = kidney failure, neurologic symptoms and others
Laboratory abnormalities seen in TTP
Microangiopathic hemolytic anemia (prominent rbc fragmentation)
Elevated indirect bilirubin
Decreased serum haptoglobin
Severely elevated LDH (lactate dehydrogenase)
Treatment of thrombocytopenic purpura
Main treatment is plasma exchange
Early diagnosis and treatment is essential
Without treatment 90% of patients die
HUS causes Endothelial damage (NOT seen in TTP) and inappropriate platelet aggregation lead to significant morbidity from
Microangiopathic hemolytic anemia
Acute kidney injury and renal failure
Thrombocytopenia
Signs and symptoms of hemolytic uremic syndrome.
Recent or current bloody diarrhea Abdominal pain Decreased urine output Hematuria Renal failure Hypertension Neurologic changes Edema
General management of HUS
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
Henoch-Schönelin purpura (HSP)
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
Four major symptoms are associated with HSP
Palpable purpura
Arthritis/arthralgias
Abdominal pain
Renal disease
HSP Treatment
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)
Hemophilia
Incidence: 1/5000
X linked recessive (predominantly males)
Females – carriers (can have some degree of deficiency)
Hemophilia Types
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
Bleeding in hemophilia
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
Treatment for hemophilia
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
von Willebrand Disease
Autosomal dominant affecting both sexes equally
Most common inherited bleeding disorder
2 main functions of von Willebrand factor
Binds platelets to form the initial platelet plug
Binds with Factor VIII to prolong it’s half life
Three distinct types of von Willebrand disease
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
von Willebrand disease Symptoms
Symptoms can occur at any age
Easy bruising, skin bleeding, prolonged bleeding from mucosal surfaces
Disseminated Intravascular Coagulation (DIC)
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
DIC Manifestations
Thrombosis and hemorrhage
Petechia, purpura, gangrene
Renal failure, liver failure
In cancer patients it can be of slow onset
DIC Labs
Thrombocytopenia Prolongation of PT and PTT Low fibrinogen Increased levels of fibrinogen degradation products (d-Dimer) Schistocytes (helmet cells)
Protein C Deficiency
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.
Protein S Deficiency
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
Antithrombin III Deficiency
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
Factor V Leiden
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
Antiphospholipid antibody
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
