The Basics
Bone marrow cell in which the platelet is derived
What is the megakaryocyte ?
Medication that results in increased von willebrand factor release from platelets with efficacy in von willebrand disease
What is desmopressin ?
also accept: DDAVP
Note: Mainstay of treatment of Von Willebrand disease is DDAVP(desmopressin, 1-deamino-8-D-arginine vasopressin). DDAVP results in release of VWF & FVIII from endothelial stores. DDAVP can be given IV or intranasal spray (1.5mg/mL). Major side effect of DDAVP is hyponatremia. In severe disease, VWF replacement can be given.Antifibrinolytic therapy using e-aminocaproic acid or tranexamic acidis an important adjunctive therapy.
Protein that functions to inactivate Von Willebrand factor and when deficient or dysfunctional results in thrombotic thrombocytopenia pupura
What is ADAMTS13 ?
Note: deficiency of (or antibodies to) metalloprotease ADAMTS13. ADAMTS13 functions to cleave & inactivate Von Willebrand Factor. Deficiency/dysfunction of ADAMTS13 leads to persistence of large VWF molecules. Result is pathogenic platelet adhesion & aggregation.
The pathophysiology of heparin induced thrombocytopenia involves antibody formation to this protein which culminates in platelet activation, thrombocytopenia, & thrombosis
What is platelet-factor 4 ?
Note: antibody formation to a complex of the platelet specific protein, platelet factor 4 (PF4), & heparin. Antiheparin/platelet factor 4 antibody can activate platelets (& monocytes, endothelial cells). Many Pts exposed to heparin develop antibodies to heparin/PF4 but do not appear to have adverse consequences. A fraction of those who develop antibodies develop thrombocytopenia & a portion of those (up to 50%) will develop thrombosis
First line therapy in patients with immune thrombocytopenia purpura and severe thrombocytopenia (platelets < 30,000 cells/uL)
What is steroids ?
Note: In patients with ITP and severe thrombocytopenia (<30,000 cell/uL), there is a risk for future bleeding and require treatment with high dose oral steroids even if they are asmypomatic. IVIG may be used alone if steroids are contraindicated or can be used in conjunction with steroids in cases requiring a more rapid increase in platelet count. The majority of patients with mild to moderate asymptomatic thrombocytopenia (>30,00 cells/uL) will have a stable and benign course and do not require treatment
The average lifespan of the platelet
What is 7 - 10 days ?
Also accept: Any amount of days between 7 - 10
Note: the average lifespan of an RBC is 120 days. The average lifespan of the platelet is 7-10 days.
Condition characterized by eczema, thrombocytopenia, and immunodeficiency
What is Wiskott - Aldrich syndrome ?
Expected laboratory values in either HUS or TTP (comment on LDH, haptoglobin, total bilirubin, reticulocyte count, PT, PTT, peripheral smear)
What is increased LDH, decreased haptoglobin, increased bilirubin level, increased reticulocyte count, normal PT, normal PTT, schistocytes on peripheral smear ?
Commonly used scoring system that predicts the likelihood of heparin induced thrombocytopenia
What is the 4 Ts score?
Surgical therapy used in the management of immune thrombocytopenic purpura that is refractory to medical management
What is splenectomy ?
Protein located in the alpha-granules of platelets that acts as an adhesion molecule binding to subendothelial collagen and platelets via the GP1B receptor
What is Von Willebrand factor ?
Note: When a blood vessel bleeds, the primary goal is to repair the damage and stop the bleeding. This occurs due to a process called hemostasis. Primary hemostasis refers to formation of a platelet plug. Von willebrand factor (protein located in alpha granule of platelet & wiebel-palade bodies of endothelial cells) binds to subendothelial collagen of the vessel wall. VWF acts as an adhesion molecule & binds platelets via the platelet GP1B receptor. Binding of VWF to platelet GP1B receptor results in platelet activation/degranulation. Platelets undergo conformational change & express ADP receptor, thromboxane A2 receptor, & GPIIBIIIA receptors on their surface & also release molecules from their granules including ADP.
Although von willebrand disease classically causes 'platelet-like' symptomatology, occasionally, levels of this coagulation factor are low enough to cause very severe bleeding
What is factor VIII ?
Lifesaving therapy in thrombotic thrombocytopenia pupura
What is plasma exchange ?
Note: Plasma exchange is the treatment of TTP. Plasma exchange should continue until platelet count is normal & signs of hemolysis are resolved for at least 2 days. Although never evaluated in clinical trials, use of glucocorticoids seems a reasonable approach (should only be used as an adjunct to plasma exchange). Other immunomodulatory therapies have been reported to be successful in refractory or relapsing TTP including rituximab, vincristine, cyclophosphamide, & splenectomy
Medication used in the treatment of heparin induced thrombocytopenia
What is argatroban ?
Also accept: dabigatran, lepirudin, bivaluridin
Note: When HIT is suspected, all heparin products should be discontinued and the patient should be switched to a direct thrombin inhibitor (i.e. argatroban, lepirudin)
Two viruses that must be ruled out before a diagnosis of immune thrombocytopenic purpura can be made
What is HIV & HCV ?
Note: Before diagnosing ITP, secondary causes must be ruled out. In Pts with asymptomatic thrombocytopenia, ITP can only be diagnosed after: H&P, CBC, peripheral smear examination, HIV, & HCV testing. In Pts >60 bone marrow aspiration should also be performed (r/o MDS). Other than history, physical exam, CBC, peripheral blood smear, and HIV and HCV testing, no other tests absolutely must be performed before diagnosis ITP.
Threshold for prophylactic platelet transfusion
What is 10, 000 cells / uL ?
This disorder, named after the Swiss pediatrician who described it, is characterized by a defect in the GPIIB/GPIIIA receptor and results in bleeding symptoms that range from minimal bruising to severe hemorrhage
What is Glanzmann's Thrombasthenia ?
This substance, produced by E.Coli O157:H7 among other bacteria, is believed to result in endothelial damage and subsequent manifestations of hemolytic uremic syndrome
What is shiga - like toxin ?
Management strategy for heparin induced thrombocytopenia type 1
What is continue heparin ?
Also accept: Observe, watch and wait
Note: Type 1 HIT is non immune heparin – induced thrombocytopenia. Non- immune HIT occurs as an immediate (usually within 48 hours), mild, and transient effect of heparin on platelets. The platelet count rarely drops to <100,000/mm3 and recovers spontaneously regardless of heparin continuation or discontinuation. The pathophysiology of type 1 HIT is not known. Type 1 HIT is not associated with an increased thrombosis risk and is not clinically significant. Thus heparin therapy should not be discontinued in these patients.
Thrombopoiesis stimulating agent & third line treatment of immune thrombocytopenic purpura
What is Romiplostim ?
Also accept: Eltrombopag
Note: Splenectomy is recommended in patients with ITP refractory to steroids or for those who require ongoing steroids to maintain an adequate platelet count. Rituximab is an alternative for patients who are either poor surgical candidates or for those who refuse surgery. Third line treatments include thrombopoiesis stimulating agents include romiplostim and eltrombopag
Pseudothrombocytopenia occurs due to blood collection in tubes containing this substance
What is ethylenediaminetetracetic acid ?
Also accept: EDTA
Note: Pseudothrombocytopenia is an in vitro artifact due to agglutination via antibodies when the calcium content is decreased by blood collection in EDTA containing tubes (used to collect blood for CBCs). Pseudothrombocytopenia occurs due to ethylenediaminetetracetic acid (EDTA)-induced platelet clumping and should be suspected in asymptomatic patients with low platelet counts. A repeat platelet count using an anticoagulant other than EDTA that shows normal platelets confirms the diagnosis.
Rare autosomal recessive disorder that results in deficiency in the GP1B receptor on platelets and characterized by thrombocytopenia, bleeding, and abnormally large platelets on peripheral smear
What is Bernard - Soulier syndrome ?
Condition of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia due to to inherited mutations of complement regulatory proteins or acquired via disorders that cause endothelial injury including APS, scleroderma, and malignant HTN
What is Atypical HUS ?
The four T's score includes these parameters
What is Timing, thrombocytopenia, oTher, thrombosis ?
Eponym describing immune thrombocytopenia pupura seen in conjunction with autoimmune hemolytic anemia
What is Evan's syndrome ?