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59 Cards in this Set

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What is normal platelet life span?
10d
Normal platelet count
150,000 - 400,000/mm^3
What is GpIIb-IIIa?
Platelet surface protein that binds to fibrinogen, which binds other platelets
Symptoms of platelet hypofunction
epistaxis
gum bleeding
bruising
heave menses
petechiae
NOT hematomas or bleeding into joints
Effects of abnormal platelet activation:
strokes
heart attacks
gangrenous limbs
When evaluating thrombocytopenia, first r/o what?
Pseudothrombocytopenia - lab artifact that must be confirmed on blood smear
Three catagories of causes of thrombocytopenia
Underproduction
Peripheral destruction
Splenic sequestration
Three causes of platelet underproduction
Marrow failure (myelodysplasia, aplastic anemia, vitamin deficiencies)
Marrow infiltration (tumors, etc)
Marrow toxins (drugs, radiation)
What are the non-immune causes of peripheral destruction of platelets?
DIC
TTP
DIC is characterized by:
1. Abnormal activation of coagulation
2. Generation of thrombin
3. Consumption of clotting factors
4. Destruction of platelets
5. Activation of fibrinolysis
How is DIC diagnosed?
1. Elevated PT
2. Elevated PTT in advanced cases
3. Low platelets
4. Low/falling fibrinogen
5. Elevated fibrin degradation products or D-Dimers
6. Few schistocytes on blood smear
Why is PT elevated in DIC?
B/c of consumption of Factor VII, which has half-life of 4 hours
What are the etiologies of DIC?
Gram negative sepsis
Severe burns
OB disasters
Certain leukemias or tumors
Shock
Insect or snake venoms
What are supportive measures that can be used to treat DIC?
Tx of platelets
Clotting factors
Fibrinogen
+/- low dose heparin to halt thrombin generation
What are the characteristics of TTP?
1. Abnormal activation of platelets and endothelial cells
2. Fibrin deposition in the microvasculature
3. Peripheral destruction of platelets and red cells
What are the diagnostic features of TTP (The Pentad)?
1. Microangiopathic hemolytic anemia (MAHA) - MUST BE PRESENT
2. Low platelets - MUST BE PRESENT
3. Fever
4. Neurological manifestations
5. Renal manifestations (hematuria, proteinuria, increased BUN/creatinine)
What are the hematological features of MAHA?
1. Elevated LDH
2. Elevated bilirubin
3. Schistocytes on the peripheral smear
What is the etiology of TTP?
Sporadic cases due to antibody against protease that cleaves ultra-large molecular weight multimers of von Willebrand's factor; ultra-large vWFs lead to abnormal platelet activation
What are drugs that can cause TTP?
Ticlopidine
Quinine
Cyclosporine
Tacrolimus
Gemcitabine
What percentage of pts that survive TTP will relapse within 10 years?
33%
What is the treatment for TTP?
Plasma Exchange
Remove all enciting agents
Should platelet transfusions be used to treat TTP?
ABSOLUTELY NOT
doing so only fuels the fire
What are the unique features of TTP/HUS?
Fewer neuro sequelae, but more renal manifestations
Usually precipitated by diarrheal illness, esp E. coli O157:H7 or Shigella
Seen more in pediatric patients
May respond less well to plasma exchange
What drugs classically induce thrombocytopenia?
1. Beta-lactam antibiotics
2. Trimethoprim-sulfamethoxazole and other sulfa drugs
3. Quinine/quinidine
4. Heparin
5. Abciximab (ReoPro)
What is the platelet response seen in HIT?
Platelets fall 30-50% 7-10d after heparin is started
PLATELET COUNTS DO NOT HAVE TO BE ABNORMAL
What is the initial treatment for ITP?
Corticosteroids (prednisone)
IVIg if more rapid therapy needed
What is the second-line therapy for ITP and how often is it needed?
Splenectomy
2/3 of pts relapse after steroid taper
What are the possible causes of splenomegaly?
1. Portal hypertension
2. Malignancy
3. Infiltrative diseases
4. Infectious diseases
5. Chronic hemolytic diseases (hemoglobin C)
What are the congenital causes of qualitative platelet disorders?
1. Glanzmann's thrombaesthenia
2. Bernard-Soulier
What are the causes of acquired causes of qualitative platelet disorders?
1. Uremia
2. Drugs (ASA, NSAIDS)
3. Herbs (ginkgo, garlic, Vit E)
4. Myeloproliferative diseases
What is the Diff Dx for eosinophilia?
NAACP
1. Neoplasm
2. Allergy/Asthma
3. Addison's disease
4. Collagen vascular disease
5. Parasites
Pale pink granular cytoplasm with condensed, segmented nucleus = ________
Neutrophil
Granulocytes with large, refractile, orange-pink granules; nucleus is typically bilobed = ________
Eosinophil
Large, dark blue granules which overlie the nucleus = ________
Basophil
Oval nucleus, with a thin rim of blue cytoplasm = ________
Lymphocyte
Folded nucleus with uneven countour; slate grey cytoplasm; there may be vacuoles = ________
Monocyte
What are the functions of PMNs?
Chemotaxis
Phagocytosis
Killing of phagocytosed bacteria
What are the functions of eosinophils?
Chemotaxis
Phagocytosis
Killing of phagocytosed bacteria
Antibody dependent damage to parasites
Regulation of immediate-type hypersensitivity reactions
What are the functions of basophils?
Mediation of immediate-type hypersensitivity responses
Modulation of inflammatory responses
What are the functions of lymphocytes?
Immune regulation and production of hematopoietic growth factors
What are the functions of monocytes?
Chemotaxis
Phagocytosis
Killing of some microbes
Antigen presentation
What are the major causes of elevated neutrophil counts?
Acute Infections
Acute Inflammation
Myeloproliferative disorders
Leukocyte adhesion deficiency
Drugs (corticosteroids, G-CSF, lithium)
S/p splenectomy
What drugs can cause neutropenia?
Anti-psychotics
Anti-epileptics
Anti-thyriod
Some antibiotics
What drugs can cause agranulocytosis?
Clozapine
Propythiouracil
Anti-convulsants
Sulfa and chloramphenicol antibiotics
What are significant non-drug causes of neutropenia?
Infection, especially with CMV
Systemic lupus erythematosus
Felty's syndrome (rheumatoid arthritis, splenomegaly, and neutropenia)
What are significant causes of lymphocytosis?
Viral infection
Bacterial infection, esp pertussis
CLL
What are significant causes of lymphocytopenia?
Immunodeficiencies (HIV/AIDS)
Immunosuppressive drugs
Lymphomas
Granulomatous diseases, including TB and sarcoidosis
What are the significant causes of acquired defects in neutrophil function?
Corticosteroid use
Alcoholism
Leukemias
Myelodysplasia
Myeloproliferative disorders
Where is von Willebrand’s factor located?
Subendothelium
Inside platelets (secreted)
What agents can activate platelets?
Thrombin
Thromboxane (TxA2)
Collagen
ADP
Epinephrine
Serotonin
What is dificient in Hemophilia A?
Factor VIII
What is dificient in Hemophilia B?
Factor IX
Hemophiliacs commonly suffer from erosion of what joint?
The knee
What is the most common hereditary bleeding disorder?
von Willebrand Disease
What are the two functions of vWF?
Carrier molecule for F.VIII
Activation of platelet adhesion
What are common causes of acquired coagulopathy?
Vitamin K deficiency (F.II, F.VII, F.IX, F.X, proteins C and S)
Liver disease
Thrombocytopenia from hypersplenism
DIC
A delayed PT indicates a deficiency or defect in what?
Fibrinogen
Prothrombin
Factor V
Factor X
Factor VII
A delayed PTT indicates a deficiency or defect in what?
Fibrinogen
Prothrombin
F.V
F.X
F.VIII
F.IX
F.XI
F.XII
What do the results of the mixing study (aPTT) indicate?
If it corrects the APTT, pt has coagulation factor deficiency
If it does not correct the APTT, pt has a factor inhibitor