Bleeding Disorders 1 Flashcards
What is the first question to ask when a patient has a bleeding disorder?
Is it a platelet problem? Or is it at coagulation problem?
2 events of the first phase of hemostasis
- Arterial vasoconstriction (endothelin mediated)
- Platelet adhesion → formation of platelet plug
Events of secondary hemostasis
- Coagulation
- Clot resorption
Classification of bleeding disorders
- Thrombocytopenia and platelet disorders
- Coagulation defects
- Fragility of vessel walls
What 2 labs would you order to determine whether the problem is platelet sarcoid relation?
- CBC
- Coagulation tests: PT, PTT
Normal number of platelets
150,000 to 400,000
Below _____ = post-traumatic bleeding; below _____= spontaneous bleeding
- 50,000
- 20,000
(platelets can function from 50,000-150,000)
Half-life of platelets
9 days
(2-3 if transfused)
Intrinsic system of coagulation is activated by _____ and involve factors _____.
- Collagen exposure
- XII, XI, IX, X
Regulation pathways converge at factor ______
X → Xa + V
The extrinsic system of coagulation is activated by ______
external trauma tissue factor
PT
Prothrombin time
PT monitors the ____ pathways by measuring the ______.
- Extrinsic and common pathways
- clotting of plasma after thromboplastin & Ca2+ ions
PTT monitors the _____ pathways by measuring the _____.
- intrinsic and common
- clotting of plasma after kaolin, cephalin & Ca2+ ions
Factor V, X, prothrombin and fibrinogen are all measured in BOTH PT & PTT, which factors are specific to the PT pathway? PTT pathway?
- VII
- VIII, IX, XI, XII
What is the main difference equation between platelets and coagulation problems clinically?
Platelet problems are mostly superficial bleeding
(skin & mucous sx)
What is the difference between petechiae, purpura and ecchymoses?
- Petechiae: 1-2 mm
- Purpura: 2mm - 1 cm
- Ecchymoses: > 1cm
These are typical of which type of general bleeding disorders?
Platelet disorders → superficial bleeding
What is the biggest threat a platelet disorders?
Intracranial bleeding
(rare, but most serious)
Once you determine the patient has a platelet dysfunction what is the next question to ask?
Too few platelets or defective platelets
4 Causes of thrombocytopenia
- Decrease survival
- Decrease production
- Sequestration
- Dilution
(MC)
Decrease production of platelets is commonly due to ______ (6).
- Aplastic anemia
- B12, folate deficiency
- Drugs/EtOH
- Infection
- Leukemia
- myelodysplastic syndrome (ineffective hematopoiesis)
How does heparin cause decreased platelet production?
anti-heparin-PF4 ab → activate platelets & pro-thrombotic state → depletion
List the drugs that can cause a decreased production of platelets (6).
- Chemotherapy
- Heparin
- Quinidine
- Radiotherapy
- Sulfur compounds
- Thiazides
Why is concomitant thrombocytopenia a common problem in cancer patients _______?
- Bleeding risk
- Thrombocytopenia limits chemotherapy schedule
In evaluating a thrombocytopenic cancer patient you must check for ______ (6).
- Coagulopathy
- Drug reactions
- Infection
- ITP
- Post-transfusion purpura
- TTP & HUS
Which chemotherapy drugs have the highest rate of inducing thrombocytopenia (2)?
- Gemcitabine
- Platinum-based regimens
How do the following chemotherapy agents → thrombocytopenia:
- alkylating agents affect ______.
- cyclophosphamide agents affect _______.
- bortezomib prevents ______.
- stem cells
- later megakaryocyte progenitors
- platelet release from megakaryocytes
(some treatments promote platelet apoptosis)
The main regulator of platelet production is ______ and is therefore used as a treatment for thrombocytopenic patients with cancer to receive chemo.
thrombopoietin
Classical causes of thrombocytopenia (decreased survival of platelets)
- ITP (immune thrombocytopenia)
- TTP
- HUS
In ITP (immune thrombocytopenia), antibodies destroy the platelets. What are the secondary causes?
- SLE
- HIV
- CLL
In ITP, IgG anti-platelet antibodies opsonize the ______.
platelets → phagocytosis of platelets/megakaryocytes in the spleen
(GpIIb/GpIIIa on platelets which mediates primary hemostasis)
ITP is most commonly seen in which patient population
women under 40
ITP s/sx
- petechiae
- mucosal bleeding (nose bleed, excessive bleeding from gums)
- ecchymoses
What is thrombotic thrombocytopenic purpura
excessive platelet activation → deposit as thrombi in small blood vessels
Pentad for TTP
Mn: “Nasty Fever Ruined My Tubes”
- N – Neurological symptoms,
- F – Fever
- R – Renal function impairment
- M – Microangiopathic hemolytic anemia
- T – Thrombocytopenia
TTP is associated with an enzyme deficiency of ______ which leads to _____.
- ADAMTS13 (vWF metalloprotease)
- vWF accumulate → platelet activation & aggregation
(acquired auto-ab or inherited)
TTP patients must avoid
transfusion of blood cells (especially platelets)
TTP tx (3)
- plasma transfusions (plasmapheresis)
- ASA & persantine
- prednisone
(blood will increase the progression of disease)
Typical HUS is caused by ______
shiga-like toxin of E. coli O157:H7
In typical HUS, shiga-like toxin of E. coli O157:H7 damages _____.
endothelial cells, activates platelets → aggregation
Symptoms of HUS
bloody diarrhea
(after HUS exposure)
Atypical HUS is caused by _____
deficiency of alternative pathway complement inhibitor (CD46 or factor I)
(inherited or acquired by antibody production)
Atypical HUS may be triggered by _____ (4).
- Rx
- Radiation
- Infection: HIV, pneumococcal
- SLE, lymphoid neoplasms
How do you distinguish from DIC & HUS?
- TTP & HUS is a platelet problem
- DIC is a coagulation + platelet problem
(PT & PTT is normal in TTP & HUS)
HUS: glomerulus w/capillary fibrin thrombi, karyorrhexis & entrapped fragmented RBCs
HUS : Diffuse glomerular basement membrane multilayering
(PAS staining)
In addition to ITP, TTP & HUS, what are the 2 other causes of thrombocytopenia?
- Sequestration of platelets in spleen
- transfusions w/non-viable platelets → dilution
Spleen findings in thrombocytopenia
normal size, but congested sinusoids & enlarged follicles
bone marrow findings in thrombocytopenia
increased number of megakaryocytes
peripheral blood findings of thrombocytopenia
megathrombocytes
