Platelets Flashcards
Role of platelets in hemostasis
Petechiae vs. purpura vs. ecchymoses
Enlarged platelets consistent w/ Bernard Soulier syndrome
What is the inheritance pattern of Bernard Soulier syndrome
Autosomal recessive disorder
associated with mutations in genes
for proteins in the platelet GPIb complex
Inheritance pattern of Glantzmann thrombasthenia
Autosomal recessive
associated with mutations in either ITGA2B or ITGB3, the genes for the two parts of the integrin αIIbβ3 receptor (GPIIb/GPIIIa)
How is Glantzmann thrombasthenia dx’d?
Flow cytometry for GPIIb/GPIIIa)
Elevated BUN
Uremia - due to renal insufficiency (NO is increased and decreases platelet binding to endothelium)
How long after aspirin Tx does it take for affected platelets to clear?
7-10 days
Inheritance pattern of May-Hegglin anomaly
Autosomal dominant
What platelet disorder is characterized by variable thrombocytopenia, giant platelets, and particularly by blue-gray cytoplasmic inclusions in neutrophils (but also in monocytes and eosinophils)
May-Hegglin anomaly
Bleeding problems arise from decreased platelet number
Blue-gray cytoplasmic inclusions (Dohle bodies) seen in May-Hegglin anomaly
What mutation causes May-Hegglin anomaly?
Mutations in the gene for myosin heavy chain (MYH9)
Platelet satellitism - artifact (does not represent actual thrombocytopenia or risk for clot formation in vivo)
Lab qualification for heparin induced thrombocytopenia
50% reduction from the pre-heparin baseline regardless of what absolute platelet count number is at that point
After at least 5-10 days on heparin therapy with no previous heparin exposure (can present within 24 hours if exposed to heparin within 30 days prior)
Stage four fibrosis
Cirrhosis
Produces portal hypertension which leads to splenomegaly
Why not perform splenectomy in splenamegaly Pt w/ cirrhosis?
Although splenectomy would resolve thrombocytopenia - altered hemodynamics of portal circulation creates extermely high risk for intra-abdominal thrombosis
After splenectomy - Pt’s w/ liver fibrosis will have a large increment in their platelet count and typically need to be Tx’d prophylactically w/ aspirin
What causes underproduction of platelets in liver disease
Loss of thrombopoietin production
TPO agent designed to temporarily raise platelet count in liver disease
Avatrombopag
Only used temporarily - long-term use results in liver fibrosis and fibrosis of marrow
Coagulopathy of liver disease
- Prolonged PT and PTT
- Underproduction of fibrinogen
- Low platelet count (decreased TPO production)
- Elevated markers of secondary fibrinolysis
- Factor VIII is normal or high
Factor VIII is consumed in DIC but not in liver disease coagulopathy
Resembles DIC except it is the result of underproduction rather than activation of coagulation causing consumption of coagulation factors
Tx of coagulopathy of liver disease
Involves raising fibrinogen and platelet count to safe hemostatic values
Not helpful to correct PT/aPTT
Pathophysiology of Immune thrombocytopenic purpura
Antiplatelet Abs that increase platelet clearance
GPia/IIa and GPIIB/IIIa are most common Ags
TPO levels are diminished
Young anemic female presents w/ isolated thrombocytopenia. No blood loss or iron deficiency are found. What is the most likely Dx?
Immune thrombocytopenic purpura
Mostly primary, but can be secondary to SLE/RA/CLL
Evans syndrome
Concurrence of ITP and autoimmune hemolytic anemia
Common for hemolytic anemia to resolve after Tx, but ITP may recur (particularly post splenectomy)
What type of thrombocytopenia has the lowest risk of bleeding at any given platelet count?
Immune thrombocytopenic purpura
Thrombocytopenia, elevated D dimer, prolonged PT/aPTT, and decreased factor VIII
DIC
Factor VIII is normal or elevated in coagulopathy of liver disease (decreased in DIC)
What causes thrombotic thrombocytopenic purpura
Deficiency of ADAMTS-13 - matrix metalloproteinase that cleaves very high molcular weight vWF multimers
Also autoimmune disease associated w/ Abs against ADAMTS-13
Diagnostic pentad of thrombotic thrombocytopenic purpura
- Microangiopathic hemolysis
- Thrombocytopenia
- Fever
- Renal findings
- Neurologic issues by Hx or physical
FAT RN
Caplacizumab
Anti-vWF mAb
Heparin induced thrombocytopenia Dx
Testing for Abs against platelet factor-4
Functional assay testing serotonin release by platelets in presence of heparin
Preferred substitute if Pt has HIT
Fondaparinux - low molecular weight heparin (all other heparin products are contraindicated)
Fondaparinux is an extremely small molecule and is apparently missing the antigenic site for HIT.
Other parenteral agents that can be used are the direct thrombin inhibitor argatroban or the non-immunogenic heparinoid, danaparoid.
If the patient has not had a cerebral vein thrombosis, then it would be reasonable to use a direct oral anticoagulants like rivaroxaban or apixaban.
What integrins are activated during platelet adhesion?
αIIbβ3 and α2β1 integrins
What is a Platelet Function Analyzer (PFA)?
A test assessing platelet function based on “closing time” (CT) under low pressure with specific agonists like collagen and epinephrine (EPI)
What does a prolonged CT-EPI but normal CT-ADP indicate?
An “aspirin-like defect” due to cyclooxygenase inhibition.
What does a prolonged CT-EPI and CT-ADP indicate?
General platelet dysfunction, seen in disorders like uremia or Glanzmann thrombasthenia
How are platelet aggregation studies performed?
Platelet-rich plasma is exposed to agonists (ADP, ristocetin, etc.), and aggregation patterns are traced via light transmission.
How does aspirin affect platelet function?
Irreversibly inhibits cyclooxygenase (COX-1), impairing TxA2 production for 7–10 days.
pseudothrombocytopenia
A laboratory artifact caused by EDTA-dependent platelet clumping in collection tubes
What diagnostic features distinguish TTP from DIC?
Normal PT/aPTT in TTP, compared to prolonged values in DIC.
What is the treatment for TTP?
Plasma exchange/plasmapheresis and immunosuppressive therapy (e.g., rituximab)
What is the preferred treatment for HIT?
Discontinuing heparin and initiating a non-heparin anticoagulant like fondaparinux or argatroban.
What is VITT?
A condition resembling HIT, occurring after adenoviral vector COVID-19 vaccines, with PF4 antibody presence and thrombosis.
Why VITT is managed with non-heparin anticoagulatns
What causes a decrease in platelet binding to endothelium in a Pt w/ renal insufficiency?
Increase NO production
Which of the following is the first step in primary hemostasis?
A. Exposed tissue factor triggers thrombin formation
B. Collagen-platelet glycoprotein (GP) VI interaction leads to release of ADP, ATP, TxA2
C. von Willebrand factor binds to exposed collagen and to platelet glycoprotein (GP) Ib
D. Activated integrins bind to collagen
C. von Willebrand factor binds to exposed collagen and to platelet glycoprotein (GP) Ib
In patients with thrombocytopenia, petechiae are most likely to be in which areas of the body?
Dependent areas (LE’s)
In patients with thrombocytopenia, petechiae are most likely to be in which areas of the body? What is the most likely Dx?
Bernard-Soulier syndrome
May-Hegglin shows no abnormality on PFA study
An asymptomatic patient is reported to have thrombocytopenia with a platelet count 45,000/uL (normal 150,000-400,000/uL). The peripheral blood smear report indicates there is platelet clumping. What test do you will order to confirm EDTA-induced platelet clumping (pseudothrombocytopenia) ?
Repeat CBC in a sodium citrate (Na-citrate) tube
What contributes to thrombocytopenia in Pt’s w/ liver disease?
-Hypersplenism
-Decreased TPO production
What is the simultaneous occurrence of AIHA and ITP referred to as?
Evan’s syndrome
Which of the following clinical features would distinguish hemolytic uremic syndrome (HUS) from thrombotic thrombocytopenic purpura (TTP)?
A. Microangiopathic hemolytic anemia
B. Thrombocytopenia
C. Renal failure requiring dialysis
C. Renal failure requiring dialysis
In TTP - ADAMTS-13 activity ~10%
Platelet aggregation studies shoes aggregation with nothing but ristoscetin, what is the likely Dx?
Glanzmann thrombosthenia
B. CT-EPI prolonged; CT-ADP normal
D. Myosin heavy chain gene mutation (mutation in MYH9 gene)
Problem w/ May-Hegglin - platelet Fx is normal, but there is low platelet #’s
What pathophysiological process causes a nonspecific effect on the GPIIb/IIIa receptor?
Uremia
Correct anemia using DDA VP to release vWF; also dialysis will Tx (also cryoprecipitate - contains vWF)
Cryoprecipitate contains what, primarily?
vWF and fibrinogen
C. Decreased factor VIII activity
Factor VIII is consumed in DIC, not liver disease induced thrombocytopenia
Isolated thrombocytopenia in liver disease is typically due to hypersplenism, reflecting _______
Portal hypertension
Why is there relatively less bleeding seen in coagulopathy of liver disease?
There is a balanced decrease in natural anticoagulants
A. Isolated thrombocytopenia in an otherwise healthy individual
Any of these situations can be associated w/ ITP, but the most common appearance is w/ an isolated appearance in a healthy individual
Infections that cause secondary ITP
Hep C. and H. pylori
HIV induced secondary ITP is more rare but does occur
Malignancy most associated w/ ITP
Chronic lymphocytic anemia (Rei stage four)
Splenomegaly in primary ITP
Splenomegaly is rarely seen in primary ITP
ITP seen secondary to SLE, splenamegaly is common
Least common immunoglobulin class seen in ITP
Mostly IgG, second = IgA
Least common = IgM (does’nt fix complement)
What mAb diminishes immunoglobulin production
Rituximab (anti CD20 mAb)
B. ADAMTS-13 activity less than 10%
A = DIC
C = HUS
D = aHUS
In which clotting disorder should you avoid transfusing w/ platelets?
Thrombotic thrombocytopenic purpura
Tx of aHUS is similar to the Tx of what syndrome that results in hemoglobinuria?
Paroxysmal nocturia hemoglobinuria
Heparin-induced thrombocytopenia
What heparins can induce HIT?
Both unfractionated heparin and LWMH
Only heparin that is incapable of inducing HIT is fondapiranux
Do Pt’s w/ HIT bleed?
NO
HIT is a prothrombotic disorder of platelet activation - they clot
Serotonin released from platelet leads to?
Platelet aggregation
What thrombotic event disqualifies DOACs?
Cerebral sinus thrombosis
