Platelet Dysfunction

Platelet Disorders

Platelet Dysfunction Part 1

How long after discontinuation of argatroban in HIT does aPTT return back to normal?

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2-3 hours

Platelet Dysfunction Part 1
Platelet Dysfunction Part 1

How long after discontinuation of argatroban in HIT does aPTT return back to normal?

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2-3 hours

Platelet Dysfunction Part 1
Platelet Dysfunction

What naturally occurring carbohydrate is fondaparinux a synthetic analog of ?

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Heparin – 5 pentasaccharide subunit of heparin that does not interact with PF4

Platelet Dysfunction
Platelet Dysfunction

How is danaproid monitored ?

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Anti-Xa levels

Platelet Dysfunction
Platelet Dysfunction

Which hirudin analog can be used for HIT management in renal failure ?

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Bivalidrudin

Platelet Dysfunction
Platelet Dysfunction

What it the target of bivalirudin ?

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Thrombin

Platelet Dysfunction
Platelet Dysfunction

What is the protein target of argatroban ?

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Thrombin

Platelet Dysfunction
Platelet Dysfunction

How is argatroban monitored ?

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aPTT

Platelet Dysfunction
Platelet Dysfunction

What percentage of patients exposed to heparin can develop HIT?

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Less than 5%

Platelet Dysfunction
Platelet Dysfunction

What defines relative thrombocytopenia versus absolute?

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More than a 50% reduction in platelet counts while still remaining in the reference range

Platelet Dysfunction
Platelet Dysfunction

In the setting of ITP, what defines severe thrombocytopenia?

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Less than 30,000/mcL

Platelet Dysfunction
Platelet Dysfunction

What defines severe thrombocytopenia?

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Less than 50,000/mcL

Platelet Dysfunction
Platelet Dysfunction

What are 3 differences between Bernard Soulier’s Disease and Glanzmann’s?

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Bernard – smear with large platelets, thrombocytopenia, no primary wave on platelet aggregation study
except with ristocetin
Glanzmann’s – normal platelets on smear, normal platelet count, only ristocetin shows primary platelet
wave

Platelet Dysfunction
Platelet Dysfunction

Which platelet aggregation study agent will show a low response in platelets with platelet storage pool
deficits?

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Collagen shows no response

Platelet Dysfunction
Platelet Dysfunction

What are 2 common causes of abnormal ADP/collagen and epinephrine/collagen results for PFA-100?

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Concurrent aspirin use, von Willebrand disease

Platelet Dysfunction
Platelet Dysfunction

How can you distinguish von Willebrand disease type 2B and platelet type VWD?

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You cannot distinguish them clinically. Genetic testing required

Platelet Dysfunction
Platelet Dysfunction

What is the median platelet count for heparin-induced thrombocytopenia?

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60,000

Platelet Dysfunction
Platelet Dysfunction

Which 3 medications can be used for heparin-induced thrombocytopenia?

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argatroban, fondaparinux, bivalirudin

Platelet Dysfunction
Platelet Dysfunction

Which anticoagulant can be used for heparin-induced thrombocytopenia if the patient has liver failure?

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Bivalirudin, as argatroban cannot be used in liver failure

Platelet Dysfunction
Platelet Dysfunction

When can you start warfarin in a patient with heparin-induced thrombocytopenia?

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When platelets are greater than 150,000

Platelet Dysfunction
Platelet Dysfunction

What is the mechanism of oxaliplatin induced thrombocytopenia?

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Immune mediated

Platelet Dysfunction
Platelet Dysfunction

Which anticoagulant pathway proteins increase thrombosis risk in heparin-induced thrombocytopenia?

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Protein C and antithrombin III

Platelet Dysfunction
Platelet Dysfunction

Which genetic syndrome leads to congenital TTP?

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Upshaw-Schulman because of low ADAMTS13

Platelet Dysfunction
Platelet Dysfunction

Which platelet receptor helps bind to the endothelial cell wall?

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Gp1b/1x

Platelet Dysfunction
Platelet Dysfunction

What is the treatment for ticlodipine/clopidogrel induced TTP?

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Ticlodipine – plasma exchange
Clopidogrel – discontinue medication and consider plasma exchange

Platelet Dysfunction
Platelet Dysfunction

What mechanism underlies Quebec platelet disorder?

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Increased urokinase plasminogen activation in platelets leading to delayed fibrinolysis bleeding

Platelet Dysfunction
Platelet Dysfunction

What is the ADAMTS13 cut-off for TTP diagnosis?

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5%

Platelet Dysfunction
Platelet Dysfunction

In what portion of gestation do you see TTP?

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Before 20 weeks

Platelet Dysfunction
Platelet Dysfunction

How can you manage uremic bleeding?

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Cryoprecipitate +/- DDAVP

Platelet Dysfunction
Platelet Dysfunction

What Platelet surface protein does Quinine bind to when it causes thrombocytopenia?

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Gp-IIb/IIIa

Platelet Dysfunction
Platelet Dysfunction

Does drug-induced thrombocytopenia cause mild, moderate or severe thrombocytopenia?

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Severe

Platelet Dysfunction
Platelet Dysfunction

What can be seen in May-Heggelin’s Disease?

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Thrombocytopenia, large platelets, cataracts, hearing loss, kidney dysfunction

Platelet Dysfunction
Platelet Dysfunction

Which gene mutation leads to May-Heggelins?

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MYH9

Platelet Dysfunction
Platelet Dysfunction

What can distinguish alloimmune thrombocytopenia of the newborn versus ITP?

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Maternal platelet count:

if normal- alloimmune thrombocytopenia
if low – ITP

Treatment = washed mother’s platelets

Platelet Dysfunction
Platelet Dysfunction

Which chromosome deletion occurs in thrombocytopenia with absent radius?

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1q21.1 deletion

Platelet Dysfunction
Platelet Dysfunction

Which platelet surface antigen is responsible for posttransfusion purpura?

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HPA-1a

Platelet Dysfunction
Platelet Dysfunction

Which ethnic group may require a dose reduction for eltrombopag ?

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East Asians

Platelet Dysfunction
Platelet Dysfunction

What is a common side effects with WhinRho for ITP?

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AIHA

Platelet Dysfunction
Platelet Dysfunction

What is the difference in plasmapheresis for TTP versus other conditions?

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Plasma versus albumin

Platelet Dysfunction
Platelet Dysfunction

What platelet concentration is a cut-off to start treatment for ITP?

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30,000

Platelet Dysfunction
Platelet Dysfunction

What are the effects of ticlodipine and clopidogrem on ADAMTS13 levels?

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Ticlodipine – suppressed
Clopidogrel – unchanged

Platelet Dysfunction
Platelet Dysfunction

What TTP-like diagnosis can be made in allogeneic stem cell transplant patients?

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Transplant associated MAHA

Platelet Dysfunction
Platelet Dysfunction Part 2

Do glucocorticoids or IVIG raise the platelet count faster for ITP?

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IVIG – nearly 80% at 5 days versus 60%

Platelet Dysfunction Part 2
Platelet Dysfunction

What are the disadvantages of high-dose pulse glucocorticoids versus lower dose tapered glucocorticoids?

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Mood alterations and insomnia

Platelet Dysfunction
Platelet Dysfunction

Which ITP patients will have the highest chance of response with anti-D immunoglobulin?

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Patients who have not had a splenectomy and are Rh+ blood type

Platelet Dysfunction
Platelet Dysfunction

In patients with pregnancy related thrombocytopenia, that require neuraxial anesthesia, what threshold is recommended ?

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More than 80,000/mcL

Platelet Dysfunction
Platelet Dysfunction

When would you consider a TPO mimetic in pregnancy related thrombocytopenia?

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Never

Platelet Dysfunction
Platelet Dysfunction

Does dexamethasone provide a quicker response than prednisone for pregnancy-induced thrombocytopenia?

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Yes

Platelet Dysfunction
Platelet Dysfunction

How can you manage thrombotic thrombocytopenic purpura in pregnancy?

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Plasma exchange

Platelet Dysfunction
Platelet Dysfunction

What percentage of thrombocytopenia during pregnancy is gestational thrombocytopenia?

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60%

Platelet Dysfunction
Platelet Dysfunction

What protein does the ELISA screen for HIT target ?

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PF4 IgG

Platelet Dysfunction
Platelet Dysfunction

Which test for HIT uses a radioactive agent?

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Serotonin release assay – uses carbon 14

Platelet Dysfunction
Platelet Dysfunction

Are men or women more likely to have heparin-induced thrombocytopenia?

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Women

Platelet Dysfunction
Platelet Dysfunction

Is heparin-induced thrombocytopenia more likely with a treatment dose of heparin versus a prophylactic dose?

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Yes

Platelet Dysfunction
Platelet Dysfunction

Does surgery increase the risk of having heparin-induced thrombocytopenia?

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Yes

Platelet Dysfunction
Platelet Dysfunction

Does low molecular weight heparin pose the same risk of forming ultra large complexes compared to unfractionated heparin?

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No, it is 10-fold less

Platelet Dysfunction
Platelet Dysfunction

Does resolution of IgG PF4 in a patient with a history of heparin-induced thrombocytopenia guarantee immune memory resolution?

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No, patients can still have another thrombotic event

Platelet Dysfunction
Platelet Dysfunction

Which type of heparin-induced thrombocytopenia has a higher nadir?

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Type I, 100,000/mcL

Platelet Dysfunction
Platelet Dysfunction

Which type of heparin-induced thrombocytopenia is more common?

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Type 1

Platelet Dysfunction
Platelet Dysfunction

Is the antibody to platelet factor IV in heparin-induced thrombocytopenia IgG or IgM?

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IgG

Platelet Dysfunction
Platelet Dysfunction

Which type of myelodysplastic syndrome can present with isolated thrombocytopenia?

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Chromosome 20q deletion

Platelet Dysfunction
Platelet Dysfunction

Which chemotherapy agents used for colon cancer can cause drug-induced thrombocytopenia?

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Irinotecan and oxaliplatin

Platelet Dysfunction
Platelet Dysfunction

When would you consider ANA testing for a new diagnosis of ITP?

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In the presence of rheumatologic symptoms

Platelet Dysfunction
Platelet Dysfunction

Which vitamins should be tested as part of a routine ITP workup?

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Vitamin B12 and folic acid

Platelet Dysfunction
Platelet Dysfunction

Can the lack of large platelets on peripheral smear exclude a diagnosis of ITP?

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No

Platelet Dysfunction
Platelet Dysfunction

What is the incidence of intracerebral hemorrhage with ITP?

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Less than 2%

Platelet Dysfunction
Platelet Dysfunction

Does the ITP incidence increase with age?

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Yes

Platelet Dysfunction
Platelet Dysfunction

Which infectious etiologies may contribute to thrombocytopenia?

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HIV, hepatitis C, CMV, VZV, Helicobacter

Platelet Dysfunction
Platelet Dysfunction

What platelet cut off defines severe ITP?

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Less than 20,000/mcL

Platelet Dysfunction
Platelet Dysfunction

What is the first line treatment for nonemergent ITP in pregnancy?

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Steroids

Platelet Dysfunction
Platelet Dysfunction

Which Public health condition has thrombocytopenia listed as an indicator condition?

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HIV

Platelet Dysfunction
Platelet Dysfunction

Which anticoagulant in blood collection tubes can cause platelet clumping?

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EDTA

Platelet Dysfunction
Platelet Dysfunction

What is the most common cause of thrombocytopenia in the intensive care unit setting?

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Sepsis

Platelet Dysfunction
Platelet Dysfunction

How long can thrombocytopenia resolution in patients with drug-induced thrombocytopenia take after discontinuation of the drug?

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1 week

Platelet Dysfunction
Platelet Dysfunction

How long can drug-induced thrombocytopenia take to develop for patients that are naïve to the offending drug?

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1-2 weeks

Platelet Dysfunction
Platelet Dysfunction

Which antiepileptic agents are associated with thrombocytopenia?

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Carbamazepine and phenytoin

Platelet Dysfunction
Platelet Dysfunction

Which antibiotics are associated with drug-induced thrombocytopenia?

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Vancomycin, rifampin, sulfamethoxazole, ampicillin

Platelet Dysfunction
Platelet Dysfunction

Which intracellular parasites can cause thrombocytopenia?

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Malaria and babesiosis

Platelet Dysfunction
Platelet Dysfunction

Can patients with hepatitis C without cirrhosis develop thrombocytopenia?

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Yes

Platelet Dysfunction
Platelet Dysfunction

Which bleeding diathesis can be associated with thrombocytopenia?

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Von Willebrand disease type 2B

Platelet Dysfunction
Platelet Dysfunction

Where is TPO synthesized?

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The liver

Platelet Dysfunction
Platelet Dysfunction

Which conditions that have thrombocytopenia are also thrombogenic?

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Heparin-induced thrombocytopenia, antiphospholipid syndrome, thrombotic microangiopathy, paroxysmal nocturnal hemoglobinuria, disseminated intravascular coagulation

Platelet Dysfunction
Platelet Dysfunction Part 3

In which conditions should one consider a classic bleeding time test?

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Severe hemostatic defects including Glanzmann’s thrombasthenia and von Willebrand disease

Platelet Dysfunction Part 3
Platelet Dysfunction

Which agents can activate platelets for a platelet aggregation study?

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ADP, epinephrine, ristocetin

Platelet Dysfunction
Platelet Dysfunction

Which illicit drug has been associated with drug-induced thrombotic microangiopathy?

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Cocaine

Platelet Dysfunction
Platelet Dysfunction

Which antipsychotic has been associated with drug-induced thrombotic microangiopathy?

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Quetiapine

Platelet Dysfunction
Platelet Dysfunction

Which chemotherapy agents have been associated with drug-induced thrombotic microangiopathy?

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Gemcitabine and oxaliplatin

Platelet Dysfunction
Platelet Dysfunction

A hereditary deficiency of which complement proteins may lead to complement mediated thrombotic microangiopathy?

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Complement factor H, complement factor H-related proteins, factor I, membrane cofactor protein

Platelet Dysfunction
Platelet Dysfunction

Which 2 bacterial species commonly cause cytotoxin mediated hemolytic uremic syndrome?

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Shigella and Escherichia coli O157:H7 and O104:H4

Platelet Dysfunction
Platelet Dysfunction

Which vitamin deficiency and the severe form may cause thrombocytopenia with hemolytic anemia?

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Vitamin B12 deficiency

Platelet Dysfunction
Platelet Dysfunction

Which infectious etiologies may cause microangiopathic hemolytic anemia ?

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HIV, rickettsial infection, fungal infection, bacterial endocarditis, parasites and red blood cells

Platelet Dysfunction
Platelet Dysfunction

Is renal injury more common with complement mediated thrombotic microangiopathy or TTP?

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Complement mediated thrombotic microangiopathy

Platelet Dysfunction
Platelet Dysfunction

What common cardiovascular complication can result in thrombotic microangiopathy with thrombocytopenia?

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Severe hypertension

Platelet Dysfunction
Platelet Dysfunction

What are the major thrombotic microangiopathy syndromes?

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Shiga toxin mediated hemolytic uremic syndrome, atypical hemolytic uremic syndrome, drug induced thrombotic microangiopathy, complement mediated thrombotic microangiopathy

Platelet Dysfunction
Platelet Dysfunction

Which immunosuppressive therapies can also be used for the management of ITP without response to other treatment regimens?

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Azathioprine, mycophenolate, cyclosporine

Platelet Dysfunction
Platelet Dysfunction

What is the challenge with using fostamatinib for ITP ?

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Lifetime treatment required, relapse after discontinuation

Platelet Dysfunction
Platelet Dysfunction

What is the target of fostamatinib ?

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Syk

Platelet Dysfunction
Platelet Dysfunction

How is avatrombopag given in patients with liver disease who will need a procedure?

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5 day course

Platelet Dysfunction
Platelet Dysfunction

Which electrolytes can reduce the absorption of eltrombopag
Polyvalent cations including magnesium and calcium iron aluminum selenium and zinc, hence do not take within 4 hours of these supplements

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Platelet Dysfunction
Platelet Dysfunction

What is the black box warning for eltrombopag ?

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Hepatotoxicity

Platelet Dysfunction
Platelet Dysfunction

What is the dosing and frequency of eltrombopag ?

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50 mg daily

Platelet Dysfunction
Platelet Dysfunction

What is the most common adverse event with romiplostim ?

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Headache

Platelet Dysfunction
Platelet Dysfunction

What is the dose range for romiplostim for ITP ?

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1-10 mcg/kg given weekly subcutaneously
Most patients typically started 2-3 mcg/kg

Platelet Dysfunction
Platelet Dysfunction

Is there an increased risk of thromboses with TPO mimetics?

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No, meta-analyses have disproven this

Platelet Dysfunction
Platelet Dysfunction

Which of the TPO mimetics is administered as an intramuscular injection?

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None, Romiplostim is given as a subcutaneous injection

Platelet Dysfunction
Platelet Dysfunction

Can one see sustained remissions after discontinuation of TPO mimetics in ITP patients?

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Yes, reports range from 30-60%
Platelet Dysfunction

Platelet Dysfunction
Platelet Dysfunction

How quickly can one generally see a response in ITP with the use of TPO mimetics ?

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7-14 days

Platelet Dysfunction
Platelet Dysfunction

What is a very rare central nervous system side effects that may occur with rituximab treatment for ITP?

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Progressive multifocal leukoencephalopathy

Platelet Dysfunction
Platelet Dysfunction

What is the typical treatment dose and frequency for ITP with rituximab?

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375 mg/m² intravenously once a week for 4 consecutive weeks

Platelet Dysfunction
Platelet Dysfunction

What is the median duration of response with rituximab for ITP patients?

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11 months

Platelet Dysfunction
Platelet Dysfunction

What percentage of ITP patients can expect a platelet count improvement of at least 50,000 with rituximab?

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More than 60%

Platelet Dysfunction
Platelet Dysfunction

Is laparoscopic or open splenectomy safer with regards to perioperative mortality rates?

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Laparoscopic

Platelet Dysfunction
Platelet Dysfunction

What predicts for an ideal response to platelet counts after splenectomy for ITP?

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Younger age

Platelet Dysfunction
Platelet Dysfunction

What percentage of patients with ITP that undergo splenectomy will see an improvement in platelet counts greater than 50,000/mcL?

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More than 80%

Platelet Dysfunction
Platelet Dysfunction

Are you more likely to have a long-term remission from splenectomy or TPO mimetic ?

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Splenectomy

Platelet Dysfunction
Platelet Dysfunction

What percentage of primary ITP patients will end up later being reclassified a secondary ITP due to the new diagnosis of a rheumatologic condition?

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Less than 10%

Platelet Dysfunction
Platelet Dysfunction

Which hematologic malignancy is commonly associated with ITP?

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CLL

Platelet Dysfunction
Platelet Dysfunction

What platelet cut-off in pregnancy would favor ITP versus gestational thrombocytopenia?

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100,000/mcL

Platelet Dysfunction
Platelet Dysfunction

What is an important blackbox warning for anti-D use in ITP?

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Acute hemolytic transfusion reaction

Platelet Dysfunction
Platelet Dysfunction

What are some of the advantages of pulse dosed dexamethasone versus tapered prednisone for ITP?

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Better overall response, better complete response at 2 weeks, fewer bleeding events the first 10 days, fewer toxicities

Platelet Dysfunction
Platelet Dysfunction

What is the dose and frequency of pulse dosed dexamethasone for ITP?

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40 mg daily for 4 days with no taper

Platelet Dysfunction
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