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49 Cards in this Set
- Front
- Back
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Bernard Soulier Syndrome
What type of disorder? What is the defect? Lab Findings? |
Function defect of platelet adhesion
Lack glycoprotein Ib on platelet
Bleeding time-increased Platelets- decreased Large platelets Normal aggregation except with ristocetin |
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von Willebrands Disease
Where is von Willebrands Factor synthesized?
Where is it stored?
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vWF is synthesized in endothelial cells and megakaryocytes
Stored in alpha granules of plts
Present in plasma |
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von Willebrands Disease-Type 1
How common is it? Status of multimers? Cause? Structural status of vWF? Lab findings? |
-Type 1 is most common -Decreased amount of all multimers (building blocks of vWF) -Possibly due to abnormal release -Structure is normal
PT- normal, APTT- increased (due to decrease in factor VIII), Bleeding time- increased(adhesion impaired) |
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von Willebrands Disease- Type 1 Antigen detection
Two types of tests |
von Willebrand Factor Antigen (vWF:Ag)
1. Quantitative plasma vWF -ELISA, Immunoelectrophoresis (IEP), Automated method utilizes latex particles
2. Separate multimers on basis of molecular size -Agarose gel electrophoresis - Crossed immunoelectrophoresis |
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von Willebrands Disease- Type 1 vWF Activity
Two types |
1. Ristocetin Induced Platelet Agglutination (RIPA) -uses platelet aggregometer -uses patient PRP - Normal except for Ristocetin -Add NP (normal pool) plasma and it will correct 2. Ristocetin Cofactor (vWF:Rco) -Uses aggregometer - uses patient's plasma and donor plts - Measures ability of patient's plasma vWF to agglutinate donor platelets in the presence of Ristocetin |
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von Willebrands Disease- Type II
Status of multimers? Cause? |
Type II (A-B, M, N)
Decrease in high M. W. multimers
Possibly due to inability to stabilize large multimers |
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von Willebrands Disease- Type III
How severe? Status of multimers? Cause? |
Most severe form
All multimers are absent
Possibly due to reduced synthesis or rapid breakdown at sites of synthesis |
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von Willebrands Disease- Platelet Type (Plt defect)
Defect? |
GP-1b has increased affinity for vWF
Platelets agglutinate and are removed |
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von Willebrands Disease Treatment |
NOT commercial factor VIII concentrate-has lost the high M. W. multimers - an intermediate purity factor VIII contains intact vWF
-Cryoprecipitate - FFP - DDAVP (Desmopressin) - induces body to release stored vWF - best for type 1 |
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Platelet Function Problem Causes |
-Autoimmune- IgI anti-plt Ab -Myeloproliferative disorders- messes with production and function of everything but RBCs -Multiple Myeloma and Waldenstrom's -Igs coating Plts and collagen fivers -Chronic liver disease -alcohol-direct toxic effects - Drugs-modify plt membrane |
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Hereditary afibrinogenemia
What type of disorder? |
Platelet aggregation |
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Uremia
What type of disorder? |
Platelet aggregation |
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Glanzmann's Thrombathenia
What type of disorder? What's the defect? Lab findings? |
Platelet aggregation disorder- Platelets lack GP IIb and IIIa
Bleed time-increased PT-normal APTT-normal Platelet count- normal Platelet aggregation- normal only with ristocetin |
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Aspirin Resistance
% of people that become resistant?
Associated with what health issues?
How to detect?
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Up to 22% of those taking aspirin become resistant to the anti-plt effect
Associated with thrombosis- higher risk of MI and stroke
Detect with platelet aggregation studies, Arachidonic acid curve-more sensitive |
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Storage Pool Diseases
What type of disorder?
What is the defect? |
Disorder of release reaction
-lack dense granules -results in abnormal aggregation |
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Hermansky-Pudlak syndrome
What type of disorder?
What is the defect? |
Disorder of release reaction
-dilation of canicular system on plt surface -swiss cheese platelets -results in deficient release rxn |
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Gray Platelet Syndrome
What type of disorder?
What is the defect? |
Disorder of release reaction
-decrease in alpha granules - alpha granules are what give platelets their grainy texture
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Wiskott Aldrich Syndrome
What type of disorder? What is the defect? |
Disorder of release reaction
-micro plts -decreased alpha and dense granules -plt sequestration-decreased plt -recurrent infections-B and T cell dysfunction -serum IgM decreased |
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Chediak-Higashi
What type of disorder? What is the defect?
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Disorder of release reaction
-lack normal dense granules |
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Aspirin therapy
What type of disorder does it cause? How? |
Disorder of release reaction
-inhibits cyclooxygenase-need for TXA2 production |
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Thrombocytosis
Normal response-AKA?
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Reactive Thrombocytosis -Response to blood loss, major surgery, childbirth, tissue necrosis, inflammatory disease, exercise, etc |
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Thrombocytosis
Myeloproliferative Disorders List 4 What type of platelet count do you see? |
PV-Polycythemia Vera CML-Chronic Myelocytic Leukemia ET-Essential Thrombocythemia -malignancy of plts. >600,000 Primary Myelofibrosis
*Usually see high plts
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Thrombocytopenia
What type of platelet numbers? Why? |
Decreased number of platelets
Due to decreased production or increased destruction |
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Fanconi Syndrome
What type of disorder? |
Decreased platelet production
Congenital Hypoplasia |
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Wiskott-Aldrich
Type of disorder? Defects? |
Decreased platelet production
Congenital Hypoplasia
-Immunodeficiency in males (T and B function) -Enhancement of surface phospholipid involved in apoptosis -Small platelets-don't release granules properly |
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May Hegglin
Type of disorder? Defects? |
Decreased platelet production
Congenital hypoplasia
-ineffective thrombopoiesis w/ large bizarre plts -most asymptomatic-some have bleeding -Dohle like bodies-bluish inclusion in neutrophil |
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Neonatal Hypoplasia
Type of disorder? Causes? |
Decreased platelet production
-newborns w/ rubella lack megakaryocytes
-Drugs ingested by mom can be toxic to fetal megakaryocytes, can recover few weeks postpartum |
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Acquired Hypoplasia
List several causes |
Irradiation Drugs Ethanol Early aplastic anemia Pernicious anemia and folate deficiency Viruses Bacterial infections Malignancies Myelodysplastic syndromes-decrease in cell lines |
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Immune Thrombocytopenia Purpura (ITP)
Type of disorder? Lab findings? |
Increased platelet destruction/ immune mechanisms/ Acquired hypoplasia
-Plt count <20,000 -Variable plt size and shape -Megakaryocyte hyperplasia -Increased bleeding time -Deficient clot retraction
Body tries to compensate for low plt count by making more but antibody is attacking and destroying plts. |
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Chronic vs Acute ITP
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Chronic has fluctuating course, bleeding episodes for days/weeks, spontaneous remissions uncommon
Acute occurs mostly in kids, usually a viral infection before, sometimes post immunization, usually self limiting-80% spontaneous remission |
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Drug induced hypoplasia
Mechanisms? Common drugs? |
-A true auto-Ab develops that is not dependent on the presence of the drug -Hapten-linkage of drug to platelet, then Ab forms -Drub-Ab complex attaches to platelet
Heparin, Quinine, Quinidine |
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Heparin
When to suspect it in a patient? HIT? |
Suspect with a 30-50% drop in PLT count
Heparin-associated thrombocytopenia -Direct non-immune mediated plt activation -Not associated with risk of thrombosis |
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Heparin
HIT How does it happen? |
Heparin-Induced Thrombocytopenia
-Patient present with thrombosis and is put on heparin -Plt count drops within 7 days
-Ab developed to Platelet Factor 4-heparin complex -Fc receptor induced plt activation, plt aggregation, release rxn, and subsequent fall in the plt count. |
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Type I HIT
When does it develop? Plt count? |
Develops 1-3 days into treatment and benign
Plt counts rarely fall below 100 x 10^3/mm3 |
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Type II HIITS
Plt counts? Possible etiology |
Low platelets: 20 x 10^3/ mm3 and thrombosis
Plt aggregates and or microparticles occlude microvasculature HIT Ab binds to heparan on the endothelial cell surface and stimulates expression of tissue factor
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Heparin Pathophysiology |
-PF-4 binds to plt after activation -Heparin complexes with PF-4 -IgG bind the PF-4/heparin complex -IgG/PF-4/heparin complex activates via the Fc receptor -Fc stimulation leads to the generation of procoagulant-rich microparticles. -Thrombin generation is upregulated increasing the patient's hypercoagulable state |
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Treatment of HIT and HITTS
First action? Types of anticoagulants? |
-Ab is only active in the presence of heparin. So take the patient off heparin and platelet count will increase
-Anticoagulant options -Coumadin -Low molecular weight heparin-not ideal 20% cross reacts -Fondaprinux-synthesized portion of heparin -Direct Xa inhibitor/ does not cross react -lepthirudin and argatroban |
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Testing HIT
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-Tests for presence of Ab in patient plasma - must be off heparin for 8 hours -Uses Plt Aggregometer -Normal Donor plts and patient PPP + dilutions of heparin -If Ab present plts will aggregate -Negative control: donor plts + Pt. PPP and saline |
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Neonatal Alloimmune Thrombocytopenia
Describe in who and how it presents |
1 in 5000 newborns-normal at birth then petechiae and purpura
Pathophysiology same as HDN (Rh disease) -Mom's Abs attack baby's platelets
Plt specific Ag absent in Mom |
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Neonatal Autoimmune Thrombocytopenia
Describe |
Mother has ITP or SLE(lupus) -means high risk delivery for the baby and mom -fetal scalp platelet test -may need to do a c section and give mom platelets |
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Non Immune Mechanisms of Platelet Destruction
List 4 |
Incidental Thrombocytopenia of Pregnancy
Preeclampsia/Eclampsia -HELLP syndrome
Thrombotic Thrombocytopenic Purpura (TTP)
Hemolytic Uremic Syndrome (HUS) |
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HELLP Syndrome
What does it stand for? What is it a variant of? Etiology? |
Hemolysis, Elevated Liver Enzymes, Low Platelet count
Life-threatening pregnancy complication considered a variant of preeclampsia
-Intravascular plt activation -Microvascular endothelial damage -Thromboxane A2 release -Vasospasm -Vascular lesions in multiple organs |
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HELLP Syndrome
Lab findings? |
Hemolysis- -Decreased Hbg and Hct -Increased LDH and bilirubin and haptoglobin -Schisctocytes on peripheral blood smear
Hepatic dysfunction- Increase in AST, ALT, and LDH
Thrombocytopenia-less than 200,000/mm3 |
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Thrombotic Thrombocytopenic Purpura
AKA? Mechanism? |
AKA: TTP
-Endothelial cell injury -Platelet thrombus forms (microthrombi) -Small plt aggregates and large vWF occlude the capillaries in organs -Large multimers of vWF are normally broken into smaller formby by protease ADAMTS13 -Body makes auto-Ab against ADAMTS13 -Rare inherited variant of TTP is caused by ADAMTS13 deficiency |
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TTP
Clinical and Lab findings? (Pentad) Treatment? |
-Hemolytic anemia with schistocytes -Thrombocytopenia(hemorrhage) -Fluctuating neurological dysfunction -Fever -Progressive renal disease -FFP, anti-platelet drub(aspirin), steroids |
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Hemolytic Uremic Syndrome
AKA? Lab Findings? (Triad) Treatment? |
AKA: HUS
-Microangiopathic hemolytic anemia (MAHA) -Thrombocytopenia-sequestered in kidney, plt aggregates -Acute renal failure -RBCs, protein and casts in urine -Dialysis, transfusion
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HUS
Resembles what disease?
How can you tell the difference? |
HUS resembles TTP
Distinguished from TTP by severeity of renal failure and lack of neurologic symptoms |
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Hereditary Vascular Disorders
Name 2 and brief description |
Hereditary Hemorrhagic Telangiectasia -Vessel walls are reduced to single layer of endothelial cells, resulting in fragile vessels
Ehlers-Danlos Syndrome -AKA-Indian Rubberman -Collagen disorder -Causes adhesion problems |
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Acquired Vascular Disorders
Name 2 and brief description |
Allergic purpura -autoimmune vascular injury -Mechanism unknown -Apparently allergic manifestations
Scurvy -Vitamin C deficiency -Decreased synthesis of collagen results in weakened capillary walls |
