Bleeding & Clotting Disorders Flashcards
Thrombocytopenia
low platelet count
- does not affect PT or aPTT
- spontaneous bleeding of small vessels (skin and mucous membranes of GI and genitourinary tracts
Chronic Immune Thrombocytopenic Purpura (ITP)
Primary (idiopathic) ITP - arises in absence of known risk factors
Secondary ITP - caused by lupus (SLE), HIV, CLL (chronic lymphocytic leukemia
- common in adult women <40 years old
- Symptoms: petechiae, ecchymoses, history of easy bruising, epistaxis, menorrhagia
Treatment: glucocorticoids
antibody formation (IgG) against glycoprotein IIb/IIIa or Ib-IX on platelets and antiplatelet antibodies act as opsonins of platelets
Acute Immune Thrombocytopenic Purpura (ITP)
symptoms occur abruptly often proceeded by a Viral Illness
- disease of childhood with equal male:female ratio
- responds to glucocorticoids
Thrombotic Thrombocytopenic Purpura
Described as: pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia (thrombi occluded in vessels damage RBCs), transient neurologic deficits, and renal failure
- caused by reduced activity of the protease ADAMTS13 which cleaves von Willebrand Factor (vWF) leading to accumulation of vWF promoting platelet activation and aggregation
- Positive for: schistocytes (RBCs sheared apart by thrombi in vessels)
- increased LDH (from lysed RBCs)
Treatment: plasma exchange
DO NOT TRANSFUSE PLATELETS: addition of more platelets leads to more thrombi
Hemolytic-uremic syndrome (HUS)
condition in which microthrombi occlude the arterioles and capillaries resulting in:
- microangiopathic hemolytic anemia
- thrombocytopenia
- acute kidney injury
- Predominantly affects children
- no neurologic symptoms (as seen in TTP)
- “Typical” HUS: commonly occurs following dysentery or gastroenteritis caused by Shiga toxin-producing E. coli
- “Atypical” HUS: defects in complement factor H, CD46, or factor I in alternative complement pathway
Von Willebrand Disease
- Autosomal Dominant
- most common inherited bleeding disorder
- deficiency or qualitative disorder of vWF which stabilizes factor VIII and promotes platelet adhesion
Symptoms: mild bleeding tendency (usually unnoticed until surgery, dental procedure, trauma, or menstruation - Mucocutaneous bleeding most common: nose bleeds, heavy periods
Treatment: DDAVP (desmopression: synthetic analog of vasopressin that releases vWF from endothelium) or Humate P (which contains factor VIII and vWF
Avoid aspirin as it inhibits cyclooxygenase
Prothrombin Time (PT)
Assesses extrinsic pathway and common pathway
- add tissue factor (phospholipid and calcium) to plasma and assess time in seconds to form clot
- used to monitor warfarin therapy
- standardized by international normalized ratio (INR)
- normal 1.0
Activated partial thromboplastin time (aPTT)
assesses intrinsic pathway and common pathway
- initiate clotting by negatively charged surface and assess time to clot
- “partial” due to absence of tissue factor
Prolongation of aPTT due to:
–heparin therapy
– specific factor inhibitor (common = inhibitor to factor VIII)
D-dimer
cross-linked fibrin generated by plasmin
- used in evaluation of thromboembolism
- negative result rules out thromboembolism**
- positive result is hard to interpret
- used in evaluation of DIC
Hemophilia A
common hereditary disease linked w/ life threatening bleeding
- deficiency in factor VIII (“co-factor” of factor IX)
- X-linked recessive
- easy bruising w/ massive hemorrhage after trauma or operations
- spontaneous hemorrhage into joints causing swelling (esp. knees)
Treatment: DDAVP (desmopressin: treats mild anemia) or Factor VIII concentrates (expensive + risk of developing antibodies to factor VIII)
Hemophilia B
deficiency in Factor IX
- clinically very similar to hemophilia A
- X-linked recessive
Treatment: Factor IX concentrates
Deficiency in Factor XII
benign disease
- no increased risk of bleeding but can prolong aPTT
Disseminated intravascular coagulation (DIC)
- intravascular thrombin formation
- deposition of fibrin in the microvasculature
- inhibitors of coagulation consumed (antithrombin III, Protein C, Protein S) but fail to control the process
- fibrinolysis intiated but insufficient to remove all fibrin
- platelet consumption
Causes: sepsis, trauma, cancer, obstetrical complications, vascular disorders, toxins
Laboratory signs:
–increased PT, aPTT (bc consumption of coagulation factors)
– increased D-dimer
– decreased platelets and fibrin
– schistocytes (fragmented RBCs)
Antiphospholipid Syndrome
autoimmune disease that increases the risk of thrombosis as a result of procoagulatory antibodies
- Common cause of acquired thrombophilia (which is associated with lupus)
- development of antibodies against plasma proteins with affinity for Beta-2 glycoprotein I
Symptoms: venous or arterial thrombosis, recurrent fetal loss, thrombocytopenia
Laboratory signs:
- positive antibody test on 2 or more occasions
- *Anticardiolipin IgG, IgM (“Lupus anticoagulant”)
- prolongs aPTT and PT even though clotting is the clinical symptom
- 1:1 mixing study does not correct
Factor V Leiden
- most common inherited thrombophilia
- point mutation in factor V causes resistance to protein C inactivation of factor V
- common presents with: venous thromboembolism
- recurrent miscarriage in 2nd trimester
