Platelet Abnormalities Flashcards
What platelet abnormality is often seen in individuals who have been on a by-pass machine?
platelets get degranulated by the by-pass machine- so may have an acquired platelet dysfunction when they come out of surgery
What is the platelet function in primary hemostasis?
- vessel injury
- exposure of collage & vWF
- platelet adhesion
- platelet activation
- platelet aggregation
- primary hemostatic plug
- stabilized by fibrin meshwork
What clinical findings are seen in platelet dysfunction or thrombocytopenia?
- petechiae
- ecchymoses
- epistaxis
- menorrhagia
- GI hemorrhage
- Gingival bleeding
- Post-partum hemorrhage
- post-operative bleeding
Identify the different types of bruising seen in the provided image. These symptoms are seen in what conditions?
platelet dysfunction or thrombocytopenia
What are the type of thrombocytopenia?
- decreased production
- decreased survival
- sequestration
- dilution
What are the types of thrombocytosis?
- reactive
- infectious/trauma
- iron deficiency
- carcinoma
- exercise
- neoplastic
- myeloproliferative
What are the causes of defective platelet function & associated conditions?
- defective adhesion (Benard-Soulier)
- defective aggregation (Glanzmann thrombasthenia)
- defective secretion (storage pool disorder)
- liver disease
- uremia
- drug
What is Mey-Hegglin Anomaly?
Inheritance pattern?
Peripheral blood smear?
hereditary thrombocytopenia disorder
autosomal dominant
normal platelet function & not associated with bleeding
- mild thrombocytopenia
- large platelets
- Dohle-like bodies in leukocytes
What mutation is seen in Benard-Soulier syndrome?
mutation in GPIb, which causes a decreased membrane GPIb-V-IX (receptor for vWF & is necessary for platelet adhesion)
Bernard-Soulier syndrome causes what type of platelet dysfunction?
inheritance pattern?
Peripheral blood smear?
defective adhesion after injury -moderate to severe bleeding
autosomal recessive
- platelets are large (like May-Hegglin, but these have impaired function)
The provided smear could be from what two conditions? How could you tell them apart?
large platelets
May-Hegglin Anomaly (platelets are functional)
Benard-Soulier syndrome (impaired adhesion)
What mutation is seen in Glanzmann Thrombasthenia?
deficiency or dysfunction in GPIIb/IIIa, a protein that binds to fibrinogen & vWF during platelet adhesion & aggregation
Glanzmann Thrombasthenia causes what type of platelet dysfunction?
inheritance pattern?
Peripheral blood smear?
defective platelet aggregation in homozygotes (heterozygotes are asymptomatic)
autosomal recessive
- normal platelet count & morphology but abnormal function
What CBC values do you see in a patient with Primary Immune Thrombocytopenic purpura (ITP)?
- severe (<20K) thrombocytopenia
- often large, immature platelets
- all other counts are normal
What is the clinical presentation of a patient with chronic Primary Immune Thrombocytopenic purpura?
Treatment?
- Female 20-40yr
- insidious onset
- mucocutaneous bleeding
- NO systemic symptoms
- NO splenomegaly
- Treatment
- corticosteroids, IVIg & sometimes splenectomy
What is the cause of chronic Primary Immune Thrombocytopenia (ITP)?
autoantibodies against platelet antigen → peripheral destruction
Why is it not helpful to test for anti-platelet antibodies in the diagnosis of ITP?
it is not sensitive nor specific
negative result does not rule out ITP
What is the cause of acute ITP?
IgG antibodies directed against GP IIb-IIIa on platelets
What is the clinical presentation of a patient with acute ITP?
usually young child
abrupt onset - triggered by viral infection (1-3 weeks prior)
Secondary ITP is associated with what conditions?
autoimmune diseases, lymphomas, viral infections (HIV, HepC) & drugs (quinidine, heparin)
What is the definition of RBC fragmentation syndrome with thormbocytopenia?
non-immune hemolytic anemia resulting from intravascular RBC fragmentation, usually within small arterioles & capillaries - possibly from artificial heart valves or ventricular assist devices
What is disseminated intravascular coagulation?
formation widespread microvascular thrombi after activationof coagulation cascade by tissue factor or mimic, resulting in microangiopathic hemolytic anemia & thrombocytopenia
body degrades newly formed fibrin → consumptive coagulopathy & bleeding diathesis
What laboratory values will you see in patient with DIC?
PT, PTT, & TT may be prolonged (sometimes normal in early stages)
low fibrinogen
elevated D-dimer
elevated FDP
What peripheral blood findings are consistent with DIC?
schistocytes
What are the causes of DIC?
major trauma (crush)
overwhelming infections
obstetric complications
mucin-secreting adenocarcinomas
prostatic surgery
venomous snake bites
What is the treatment for DIC?
eliminate underlying cause
supportive therapy
What is the treatment for DIC?
eliminate underlying cause
supportive therapy
What are the the characteristics of the related Thrombotic Microangiopathies (TTP/HUS)?
diffuse microvascular occlusion of arterioles & capillaries by thrombi - mainly by platelets not fibrin
leading to blood schistocytosis, ischemia, & end organ damage
no perivascular inflammation
TTP & HUS usually have what type of coagulation screening tests?
usually normal
Thrombotic Thrombocytopenic Purpura is characterized by what features?
- severe thrombocytopenia (<20,000)
- microangiopathic hemolytic anemia (schistocytes)
- neurologic symptoms
- fever
- increased serum LDH
What symptoms is seen more commonly in TTP than other types of TMA?
systemic manifestation of organ damage (besides kidneys)
What are the two types of TTP?
Which is more common?
Age group most commonly affected by each?
inherited - uncommon (infancy & childhood - remits & relaplse)
acquired - adults & older children - single acute episode
What molecular deficiency is seen in TTP? How does this lead to its clinical presentation?
- Severe deficiency (<10%) ADAMTS13, which is responsible for cutting vWF into smaller, less reactive multimers
- Patients with this deficiency release ultra-large von Wilibrand multimers (ULvWF) after endothelial damage, leading to exuberant formation of platelet microthrombi in microcirculation
What laboratory features are consistent with TTP?
- schistocytes
- thrombocytopenia
- increased LDH
- coagulation tests are usually normal
What is the treatment for TTP?
emergent plasma apheresis with FFP or cryo-poor plasma
NO PLATELETS UNLESS LIFE-THREATENING BLEEDING
Hemolytic Uremic Syndrome is characterized by what features?
- microangiopathic hemolytic anemia
- thrombocytopenia
- acute renal failure
- +/- diarrhea
- CNS symptoms
What are the two types of Hemolytic Uremic Syndrome?
- primary “atypical” - complement dysregulation
- complement gene mutations
- antibodies to complement factor H
- secondary
- infection (shiga toxin)
- drug toxicity
- rarely - pregnancy & autoimmune
Does TTP or HUS have a lower mortality rate?
HUS has a lower mortality rate than TTP
What is the most common cause of HUS?
E. coli O157:H7
via contaminated hamburger
What is the treatment for HUS?
supportive - with dialysis
What is a common complication of unfractionated heparin?
life-treatening venous or arterial thrombosis
What are the two types of Heparin-Induced Thrombocytopenia (HIT)? What are their different features & clinical significance?
- Type I
- rapidly after administration
- direct platelet-aggregating
- usually little clinical significance
- Type II
- 5-14 days after administration
- autoantibodies to a complex of heparin & low molecular weight proteins (platelet factor 4), which activates platelets and leads to thrombocytopenia & thrombosis
- Thrombi in arteries & veins
What value should you be sure to check before stating someone on heparin?
platelet
What are two major clues to the presence of HIT?
- fall in platelet count 1-2 weeks after starting heparin
- unexpected shortening of aPTT
- still prolonged, b/c on heparin, but shorter than expected
What differential diagnoses must be ruled out as a cause of thrombocytopenia before making a diagnosis of HIT?
bleeding, infection, hemodilution
How do you confirm the diagnosis of HIT?
heparin-platelet antibody assay
do not wait for results to start therapy
What is the treatment for HIT?
stop heparin - use different anticoagulant (NOT low molecular weight heparin)
avoid giving platelets
What is the most common cause of drug induced acquired disorder or platelet function?
aspirin
(NSAID, penicillins, hydroxychloroquine, amitriptyline, etc)
What are common causes of acquired disorders of platelet dysfunction other than drug-induced?
liver disease
uremia (reversible)
bypass surgery
autoimmune disorders
hematolymphoid neoplasms
Aspirin impacts what molecule that leads to impairment of primary hemostasis?
acetylates platelet COX → impairs prostaglandin metabolism → impairs synthesis of thromboxane A2 → impairs thromboxane A-2-dependent platelet aggregation (primary hemostasis)
How does aspirin affect the coagulation cascade?
aspirin has no effect on the coagulation cascade
What effects does uremia have on platelet function?
- defects in adhesion
- decreased synthesis of thromboxane A2
- possibly circulating metabolites or toxins inhibit platelet function
What is the treatment for uremia-induced platelet dysfunction?
dialysis
DDAVP (vasopressin)
estrogens
What effects does liver diseasehave on platelet function?
- multifactorial
- FDP compromise platelet function & impair release of platelet factor 3
What effects does bypass surgery have on platelet function?
- cause thrombocytopenia & platelet dysfunction secondary to depletion of platelet dense granules & alpha granules
What are the common causes of pseudothrombocytopenia?
platelet aggregates from traumatic blood draw or inadequate mixing
EDTA-induced aggregation (draw in heparinzed tube)
After a CBC indicates thrombocytopenia, what step should occur before starting the transfusion?
peripheral blood smear review by technologist to look for platelet clumps & satelliotisis where platelets accumulate around WBC
