BLEEDING AND THROMBOTIC DISORDERS Flashcards
This deck covers bleeding and thrombotic disorders
What’s your diagnosis?
Child
Abrupt onset of petechiae/ecchymoses around 1-2 weeks after viral illness
BT-Prolonged
Platelet count- low
PT- normal
PTT- normal
The bone marrow aspirate shows an increase in immature megakaryocytes
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Acute immune thrombocytopenic purpura (ITP)
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Vitamin K dependent coagulation factors
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II, VII, IX and X
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- Inherited thrombotic disorder caused by replacement of arginine by glutamine at position 506.
- Which coagulation factor levels are increased in this disorder as a result of the single base change?
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- Factor V Leiden
- Factor Va
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List the causes for DIC
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STOP Making Thrombi
- Sepsis (gram negative)
- Trauma
- Obstetric complications
- Pancreatitis
- Malignancy
- Transfusion
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List some antiphospholipid antibodies
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anticardiolipin antibodies
anti-β2-glycoprotein antibodies
lupus anticoagulants
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- Does heparin prolong PT or PTT ?
- How?
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- Prolongation of PT and PTT
Gotcha ;)
- Heparin activates ATIII- this in turn inhibits both sides of the coagulation cascade – VIIa, IXa, Xa, XIa and thrombin
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A 56 year old female with atrial fibrillation is started on a drug. 2 days later , she develops a lesion on her left lower limb as seen below. PT is prolonged.
1. What is the reason for the development of the lesion?
2. If this woman had an inherited Protein C deficiency, would she have a greater risk of developing this lesion?
Deborah Dalmeida MD
- Warfarin induced skin necrosis
- Protein C together with Factor VII has the shortest half life (6 and 14 hours respectively). In normal individuals, the fall in protein C activity following the start of warfarin is generally not of clinical significance, but in heterozygotes with levels of protein C that are about half of normal, a further drop in protein C activity during the first day of therapy can trigger thrombosis in the skin.
Deborah Dalmeida MD
Following platelet activation, Glycoprotein IIb/IIIa located on the surface of a platelet is able to cross link with another platelet via binding to which substance?
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Fibrinogen
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dyspnea, acute renal failure
BT-prolonged
Platelet count- Low
PT- Prolonged
PTT-Prolonged
Fibrinogen- decreased1.
1.Diagnosis?
2. Most sensitive screen?
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- DIC
- Elevated D-Dimers
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1. Diagnosis?
Neurologic symptoms
Fever
Kidney Failure
BT-Prolonged
Platelet count- Low
PT- Normal
PTT- Normal
2. Etiology?
Deborah Dalmeida MD
- Thrombotic Thrombocytopenic Purpura (TTP)
- Deficiency of ADAMTS13
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How does heparin cause life threatening thrombosis?
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- large complexes of IgG, PF4, and heparin detach from platelets, , attach to endothelial cells, and damage the endothelial cells, causing activation of the coagulation system
- Enhances AT III’s affinity for thrombin, IXa,Xa, XIa and XIIa
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glomerular capillaries occluded by microthrombi
renal failure
Schistocytes on a peripheral smear
BT- Prolonged
Platelet count- Low
PT- Normal
PTT- Normal
history of bloody diarrhea after eating an undercooked hamburger at a restaurant
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HUS
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2 properties of antiphospholipid antibodies
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a. Bind to phospholipid surface
b. bind to the phospholipid part of the PTT reagent
Deborah Dalmeida MD
Bernard Soulier/ vW disease?
BT- Prolonged
Platelet count-Low
PT- Normal
PTT- Normal
reduced ristocetin cofactor activity which does not normalize after the addition of normal plasma
Deborah Dalmeida MD
Bernard-Soulier syndrome
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superficial bleeding localized to skin and mucous membranes
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Purpura
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3 examples of malignancy associated with thromboses
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Trousseau Syndrome i.e migratory superficial thrombophlebitis
Thrombosis with chronic DIC
Nonbacterial thrombotic (marantic) endocarditis
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Mechanism of heparin induced thrombocytopenia
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Drug + PF 4 = antigenic complex which reacts with antibodies–> immune complex–> bind to platelet Fc receptor –>platelet activation
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- One test that you will perform to distinguish decreased production from increased destruction of a coagulation factor
- Explain the steps and interpretation of mixing studies.
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- Mixing studies
2.
Procedure: Normal plasma mixed with patient plasma
Interpretation:
a. Correction of the PT and/or PTT indicates decreased production of coagulation factors.
b. No correction of the PT and/or the PTT indicates immune destruction of coagulation factors is present. Antibody is also destroying the coagulation factor in the normal plasma that is added to the test tube.
Deborah Dalmeida MD
easy bruising
recurrent joint bleeds
BT- Normal
Platelet count- Normal
PT- Normal
PTT- Prolonged
What are the chances of a female heterozygous carrier with a normal male partner, conceiving an affected son?
Deborah Dalmeida MD
50%
The diseases is Hemophilia A , X-linked recessive
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Defect assoc with Bernard Soulier?
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inherited deficiency of the platelet membrane glycoprotein complex Ib-IX.
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Consequence of a single base substitution in the 3′ untranslated region of the prothrombin gene
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30% higher plasma levels of structurally normal prothrombin
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Young female
malar rash, renal failure
PS- Thrombocytopenia
PTT – Prolonged
Mixing study – does not correct the PTT
Kidney biopsy- Glomeruli show multiple capillary and arterial thromboses
Diagnosis?
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ANTIPHOSPHOLIPID ANTIBODY SYNDROME
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2 to 5-mm mm, red or purple macules (spots); in the distal lower extremities ,conjunctiva and palate
Deborah Dalmeida MD
Petechiae
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Can you recall 2 examples of “inhibitors”
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Factor VIII antibodies (most common)
antiphospholipid antibodies
Deborah Dalmeida MD
Consequence of microthrombi formation in DIC
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tissue hypoxia and infarction
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Give one word that describes this :
Circulating antibodies that destroy specific coagulation factors
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Inhibitors
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Why do women with APLA have recurrent miscarriages?
Deborah Dalmeida MD
Due to antibody-mediated inhibition of t-PA activity necessary for trophoblastic invasion of the uterus
Deborah Dalmeida MD
1. What’s your diagnosis?
Young adult, female
Insidious onset of petechiae, ecchymoses
BT- Prolonged
Platelet count- Low
PT - Normal
PTT- Normal
The bone marrow aspirate shows an increase in immature megakaryocytes
- What are the antibodies detected?
Deborah Dalmeida MD
- Chronic Immune Thrombocytopenic Purpura (ITP)
- autoantibodies directed against platelet membrane glycoproteins IIb-IIIa or Ib-IX
Deborah Dalmeida MD
Why is PT/INR used to monitor patients on warfarin?
Deborah Dalmeida MD
Among all Vit K dependent coag factors Factor VII has the shortest half life.
So if you give a patient Coumadin, the first factor to show a decrease in activity will be factor VII (the others will drop off too, but not until later on).
it’s best to monitor therapy by taking a look at the extrinsic pathway (using the PT/INR), since that’s the pathway that will be affected first.
Deborah Dalmeida MD
Defect assoc with Glanzmann thrombasthenia
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deficiency or dysfunction of glycoprotein IIb-IIIa
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cause of hemorrhage in DIC
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depletion of factors required for hemostasis and the activation of fibrinolytic mechanisms
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Primary versus secondary antiphospholipid syndrome
Deborah Dalmeida MD
Primary antiphospholipid syndrome :
- manifestations of a hypercoagulable state
- No evidence of other autoimmune disorders;
- happens in association with certain drugs or infections.
Secondary antiphospholipid syndrome : seen in individuals with a well-defined autoimmune disease, such as systemic lupus erythematosus
Deborah Dalmeida MD
Bernard Soulier/ vW disease?
BT- Prolonged
Platelet count-Normal
PT- Normal
PTT- Prolonged
reduced ristocetin cofactor activity which normalizes after the addition of normal plasma
Deborah Dalmeida MD
vW disease
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Individual with known parenchymal liver disease
ecchymoses, easy bruisability
BT- Normal
Platelet count- Normal
PT- Prolonged
PTT- Prolonged
Fibrinogen - Normal
1. Diagnosis?
- Name the special poikilocyte seen on the peripheral smear. What history given above explains its appearance on the smear?
Deborah Dalmeida MD
- Vitamin K deficiency
- Acanthocyte- if due to severe liver disease
Deborah Dalmeida MD
Very large, purpuric lesions
Deborah Dalmeida MD
Ecchymoses
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Why do individuals with antiphospholipid antibodies exhibit prolonged PTT?
Deborah Dalmeida MD
The autoantibodies also just happen to bind to the phospholipid part of the PTT reagent . Then there’s not enough usable reagent in the test tube, and the patient’s specimen doesn’t clot! The coagulation tests are therefore falsely prolonged.
Deborah Dalmeida MD
