PLT DISORDERS Flashcards
What is the most common noniatrogenic cause of thrombocytopenia?
A) Immune disorders
B) Infections
C) Chemotherapy
D) Herbal medications
Correct Answer: B) Infections
Rationale: Infections are identified as the most common noniatrogenic cause of thrombocytopenia, as they can directly affect platelet production and survival through various mechanisms, including immune processes.
Which of the following is true regarding immune-mediated thrombocytopenia in children?
A) It is usually drug-induced.
B) It frequently requires prolonged treatment.
C) It often resolves spontaneously after a viral infection.
D) It is more common in adults.
Answer: C) It often resolves spontaneously after a viral infection.
Rationale: Immune-mediated thrombocytopenia in children typically follows a viral infection and resolves on its own. It is less common in adults, where the association between infection and immune thrombocytopenia is less clear.
What is the typical timeline for thrombocytopenia caused by drug-dependent antibodies?
A) Immediate, occurring within hours of exposure
B) Delayed, occurring after 21 days of exposure
C) Persistent, lasting for months after drug withdrawal
D) None of the above
Answer: B) Delayed, occurring after 21 days of exposure
Rationale: Drug-dependent thrombocytopenia usually manifests after an initial exposure period, with a median of 21 days. It generally resolves within 7–10 days after the drug is withdrawn.
Which drug class is most associated with rapid-onset thrombocytopenia (within 24 hours)?
A) Chemotherapeutic agents
B) Platelet Gp IIb/IIIa inhibitors (e.g., abciximab)
C) Quinine
D) Sulfonamides
Answer: B) Platelet Gp IIb/IIIa inhibitors (e.g., abciximab)
Rationale: Platelet Gp IIb/IIIa inhibitors like abciximab can cause thrombocytopenia within 24 hours of initial exposure, unlike other drugs, which usually take longer to induce this condition.
What distinguishes heparin-induced thrombocytopenia (HIT) from other types of drug-induced thrombocytopenia?
A) It is usually associated with severe bleeding.
B) Thrombocytopenia is mild and increases the risk of thrombosis.
C) It primarily occurs with low-molecular-weight heparin (LMWH).
D) It results in pancytopenia and bone marrow suppression.
Answer: B) Thrombocytopenia is mild and increases the risk of thrombosis.
Rationale: HIT is characterized by mild thrombocytopenia (nadir counts rarely <20,000/μL) and an increased risk of thrombosis, rather than bleeding. This sets it apart from most other drug-induced thrombocytopenias.
What is the primary mechanism behind HIT?
A) Direct destruction of platelets by heparin
B) Immune activation due to antibodies targeting platelet glycoproteins
C) Antibody formation against the platelet factor 4 (PF4) and heparin complex
D) Activation of B cells causing pancytopenia
Answer: C) Antibody formation against the platelet factor 4 (PF4) and heparin complex
Rationale: HIT is caused by antibodies against a complex of platelet factor 4 (PF4) and heparin. These antibodies activate platelets and other components of the coagulation system, increasing the risk of thrombosis.
Which type of heparin is more likely to cause HIT?
A) Unfractionated heparin (UFH)
B) Low-molecular-weight heparin (LMWH)
C) Synthetic heparin derivatives
D) All types of heparin have equal risk
Answer: A) Unfractionated heparin (UFH)
Rationale: HIT is more common with UFH than with LMWH, although both can trigger the condition. UFH has a higher likelihood of inducing antibody formation.
What is the typical time frame for the development of HIT after heparin exposure?
A) Within 24 hours of initial exposure
B) 2–5 days after initial exposure
C) 5–14 days after initial exposure
D) More than 30 days after initial exposure
Answer: C) 5–14 days after initial exposure
Rationale: Most cases of HIT occur 5–14 days after starting heparin. However, it can occur earlier if the patient was previously exposed to heparin within the past ~100 days.
What is the role of the “4T’s” scoring system in diagnosing HIT?
A) It confirms the diagnosis of HIT in all cases.
B) It excludes HIT in patients at low clinical risk.
C) It eliminates the need for laboratory testing.
D) It is only used in postoperative patients.
Answer: B) It excludes HIT in patients at low clinical risk.
Rationale: The 4T’s (thrombocytopenia, timing of platelet count drop, thrombosis, and exclusion of other causes) help to exclude HIT in low-risk cases. However, it may overdiagnose HIT in settings where thrombocytopenia and thrombosis are common (e.g., ICU).
Which rare condition mimics HIT but can occur without heparin exposure?
A) Delayed-onset HIT
B) Vaccine-induced immune thrombocytopenia and thrombosis (VITT)
C) Autoimmune thrombocytopenic purpura
D) Idiopathic thrombocytopenia
Answer: B) Vaccine-induced immune thrombocytopenia and thrombosis (VITT)
Rationale: VITT is a syndrome similar to spontaneous HIT but occurs without prior heparin exposure, most commonly after certain COVID-19 vaccinations (e.g., ChAdOx1-S/nCoV-19 vaccine).
Why should laboratory testing for HIT be limited to intermediate- or high-risk cases?
A) Anti-heparin antibodies are always diagnostic of HIT.
B) Many patients develop antibodies without clinical HIT.
C) ELISAs are highly sensitive and specific for HIT.
D) Platelet counts normalize quickly without intervention.
Answer: B) Many patients develop antibodies without clinical HIT.
Rationale: Many patients exposed to heparin develop anti-heparin antibodies, but only a fraction develop clinical HIT. Therefore, testing is recommended only for intermediate- or high-risk patients to avoid overdiagnosis
Which of the following anticoagulants is FDA-approved for treating HIT with thrombosis (HITT)?
A) Argatroban
B) Fondaparinux
C) Bivalirudin
D) Direct oral anticoagulants (DOACs)
Answer: A) Argatroban
Rationale: The direct thrombin inhibitor (DTI) argatroban is FDA-approved for treating HITT. Fondaparinux and bivalirudin are effective but not FDA-approved, and DOACs are under investigation for this indication.
Why should LMWH be avoided in the treatment of HIT?
A) It is less effective than unfractionated heparin (UFH).
B) HIT antibodies cross-react with LMWH.
C) LMWH significantly increases bleeding risk.
D) LMWH is ineffective in preventing thrombosis.
Answer: B) HIT antibodies cross-react with LMWH.
Rationale: The anti-heparin/PF4 antibodies that cause HIT cross-react with LMWH, making it unsuitable for use in treating HIT.
How long is anticoagulation typically continued in patients with HIT and thrombosis?
A) 1–2 months
B) 3–6 months
C) Until platelet count normalizes
D) Indefinitely
Answer: B) 3–6 months
Rationale: Anticoagulation is typically continued for 3–6 months in patients with HIT and thrombosis. In patients without thrombosis, the duration is less well-defined but is generally shorter.
Which rare complication of COVID-19 vaccination resembles HIT?
A) Vaccine-induced immune thrombocytopenia and thrombosis (VITT)
B) Autoimmune thrombocytopenic purpura
C) Idiopathic thrombocytopenia
D) Hemolytic uremic syndrome
Answer: A) Vaccine-induced immune thrombocytopenia and thrombosis (VITT)
Rationale: VITT is a rare syndrome similar to HIT, occurring after certain COVID-19 vaccines (e.g., ChAdOx1-S/nCoV-19). It is characterized by high D-dimer levels and unusual thrombotic events.
What is the primary mechanism underlying ITP?
A) Platelet activation and aggregation
B) Immune-mediated platelet destruction and inhibition of release from megakaryocytes
C) Bone marrow failure
D) Platelet sequestration in the spleen
Answer: B) Immune-mediated platelet destruction and inhibition of release from megakaryocytes
Rationale: ITP is caused by immune-mediated destruction of platelets, often involving autoantibodies, and may also inhibit platelet release from megakaryocytes.
In children, ITP most commonly occurs:
A) As a chronic condition with a relapsing course
B) Following an infection and is usually self-limiting
C) After administration of heparin therapy
D) With an associated autoimmune disorder like SLE
Answer: B) Following an infection and is usually self-limiting
Rationale: In children, ITP often follows a viral infection and is usually acute and self-limited, resolving spontaneously within a few weeks or months.
Which of the following is considered a secondary cause of ITP?
A) Systemic lupus erythematosus (SLE)
B) Viral infections like HIV or hepatitis C
C) Helicobacter pylori infection
D) All of the above
Answer: D) All of the above
Rationale: Secondary ITP is associated with underlying disorders such as autoimmune diseases (e.g., SLE), infections (e.g., HIV, hepatitis C), and possibly H. pylori, though its association is geographically variable.
What is the diagnostic hallmark of ITP on peripheral blood smear?
A) Large platelets with normal blood cell morphology
B) Fragmented red blood cells (schistocytes)
C) Hypochromic microcytic red blood cells
D) Neutrophil hypersegmentation
Answer: A) Large platelets with normal blood cell morphology
Rationale: Peripheral blood smears in ITP typically show large platelets due to increased bone marrow activity, with otherwise normal cell morphology.
Which laboratory test should be performed to rule out combined autoimmune hemolytic anemia and ITP (Evans’ syndrome) in anemic patients?
A) Direct antiglobulin test (Coombs’ test)
B) Serum ferritin levels
C) Platelet aggregation assay
D) Enzyme-linked immunosorbent assay (ELISA)
Answer: A) Direct antiglobulin test (Coombs’ test)
Rationale: The direct antiglobulin (Coombs’) test is used to identify autoimmune hemolytic anemia, which can coexist with ITP in Evans’ syndrome.
In adults, what is the typical course of ITP?
A) Acute and self-limiting
B) Chronic, though some may experience spontaneous remission
C) Always associated with infections like HIV
D) Rapidly fatal if untreated
Answer: B) Chronic, though some may experience spontaneous remission
Rationale: In adults, ITP often has a chronic course, but spontaneous remission can occur within months of diagnosis in some cases.
In patients with ITP, treatment is NOT immediately necessary if:
A) Platelet count is <5,000/μL
B) Platelet count is >30,000/μL without significant bleeding symptoms
C) Retinal hemorrhages are present
D) Oral mucosal hemorrhages are observed
Answer: B) Platelet count is >30,000/μL without significant bleeding symptoms
Rationale: Patients with platelet counts >30,000/μL and no significant bleeding symptoms generally do not require immediate treatment, as their mortality risk from thrombocytopenia is low.
Which of the following tests is recommended to evaluate secondary causes of ITP?
A) Hepatitis C and HIV testing
B) Bone marrow biopsy for all patients
C) CT scan of the abdomen and pelvis
D) Coagulation profile
Answer: A) Hepatitis C and HIV testing
Rationale: Secondary causes of ITP should be evaluated with tests for HIV and hepatitis C, as these are common underlying conditions.
Which corticosteroid regimen is commonly used as the initial outpatient treatment for ITP?
A) Prednisone 1 mg/kg or dexamethasone 40 mg daily for 4 days
B) Methylprednisolone 1 g daily for 3 days
C) Hydrocortisone 100 mg every 8 hours
D) Budesonide 9 mg daily
Answer: A) Prednisone 1 mg/kg or dexamethasone 40 mg daily for 4 days
Rationale: Prednisone and high-dose dexamethasone are standard initial treatments to suppress immune-mediated platelet destruction.
Rh0(D) immune globulin is appropriate for:
A) Patients with Rh-negative blood
B) Patients with Rh-positive blood
C) Patients with severe hemolysis
D) Patients with a history of splenectomy
Answer: B) Patients with Rh-positive blood
Rationale: Rh0(D) immune globulin is effective in Rh-positive patients, as it works by inducing limited hemolysis and blocking Fc receptor function.
What is the recommended treatment for severe ITP with bleeding symptoms?
A) Observation and outpatient management
B) High-dose glucocorticoids and IVIgG or anti-Rh0(D) therapy
C) Rituximab as a first-line treatment
D) Immediate splenectomy
Answer: B) High-dose glucocorticoids and IVIgG or anti-Rh0(D) therapy
Rationale: Severe ITP with bleeding symptoms requires combined-modality therapy, including high-dose glucocorticoids and immunoglobulin therapies, to quickly raise platelet counts.
Splenectomy is reserved for patients with ITP who:
A) Relapse after tapering glucocorticoids
B) Have platelet counts >50,000/μL
C) Are Rh-negative
D) Show a response to IVIgG therapy
Answer: A) Relapse after tapering glucocorticoids
Rationale: Splenectomy is an option for patients whose ITP relapses after initial treatment with glucocorticoids or other therapies, although delaying splenectomy may be reasonable to observe for spontaneous remission.
Rituximab in ITP treatment targets which type of cell?
A) T lymphocytes
B) Megakaryocytes
C) B lymphocytes
D) Reticulocytes
Answer: C) B lymphocytes
Rationale: Rituximab is an anti-CD20 antibody that targets B cells, reducing antibody production and helping to control refractory ITP.
Which laboratory finding is characteristic of microangiopathic hemolytic anemia (MAHA) in thrombotic thrombocytopenic microangiopathies?
A) Elevated platelet count
B) Decreased lactate dehydrogenase (LDH)
C) Fragmented red blood cells (schistocytes) on peripheral blood smear
D) Increased haptoglobin
Answer: C) Fragmented red blood cells (schistocytes) on peripheral blood smear
Rationale: The presence of fragmented RBCs (schistocytes) on a peripheral blood smear is a hallmark of MAHA, which occurs in thrombotic thrombocytopenic microangiopathies.
What is the key pathophysiologic defect in TTP?
A) Hyperactive platelet production
B) Deficiency of or antibodies to ADAMTS13
C) Overproduction of von Willebrand factor (VWF)
D) Autoimmune destruction of red blood cells
Answer: B) Deficiency of or antibodies to ADAMTS13
Rationale: TTP is caused by a deficiency of or antibodies to the metalloprotease ADAMTS13, which cleaves ultra-large von Willebrand factor multimers. These multimers promote platelet adhesion and aggregation.
Which ADAMTS13 activity level is diagnostic of TTP?
A) >50%
B) 30–50%
C) 10–30%
D) <10%
Answer: D) <10%
Rationale: ADAMTS13 activity levels below 10% are diagnostic of TTP.
What is the cornerstone of TTP treatment?
A) Platelet transfusion
B) Therapeutic plasma exchange (TPE)
C) High-dose glucocorticoids
D) Caplacizumab monotherapy
Answer: B) Therapeutic plasma exchange (TPE)
Rationale: Therapeutic plasma exchange is the mainstay of TTP treatment and is continued until the platelet count normalizes and hemolysis resolves.
What role does caplacizumab play in the treatment of TTP?
A) It inhibits the production of ADAMTS13 antibodies.
B) It acts as an anti-von Willebrand factor (VWF) nanobody.
C) It stimulates platelet production.
D) It replaces missing ADAMTS13 enzyme.
Answer: B) It acts as an anti-von Willebrand factor (VWF) nanobody.
Rationale: Caplacizumab is an anti-VWF nanobody that reduces platelet adhesion and aggregation in TTP, decreasing mortality and the burden of care.
What additional therapy is often used alongside TPE in the treatment of TTP to reduce relapses?
A) High-dose IV iron
B) Rituximab
C) Intravenous gamma globulin (IVIG)
D) Eltrombopag
Answer: B) Rituximab
Rationale: Rituximab, an anti-CD20 antibody, is used as an adjunct to TPE to reduce the duration of TPE and decrease relapse rates in TTP.
What are the three hallmark features of Hemolytic-Uremic Syndrome (HUS)?
A) Macrocytic anemia, renal failure, thrombocytopenia
B) Acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia
C) Fever, thrombocytosis, renal failure
D) Hematuria, leukopenia, fever
Answer: B) Acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia
Rationale: HUS is characterized by the triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia.
Which of the following is the most common etiologic agent of diarrhea-associated HUS?
A) Shigella dysenteriae
B) Campylobacter jejuni
C) Escherichia coli O157:H7
D) Salmonella enterica
Answer: C) Escherichia coli O157:H7
Rationale: E. coli O157:H7 is the most frequent causative agent of diarrhea-associated HUS, often linked to hemorrhagic diarrhea.
What distinguishes atypical HUS (aHUS) from diarrhea-associated HUS?
A) aHUS has lower mortality rates.
B) genetic defects in complement regulatory proteins cause aHUS.
C) aHUS is more commonly associated with E. coli O157:H7 infections.
D) aHUS primarily occurs in children.
Answer: B) aHUS is caused by genetic defects in complement regulatory proteins.
Rationale: Atypical HUS is linked to genetic defects or antibodies affecting complement regulation, leading to chronic complement activation.
What is the primary treatment for diarrhea-associated HUS?
A) Plasma exchange
B) Antibiotics to target E. coli
C) Supportive care, including dialysis as needed
D) Eculizumab
Answer: C) Supportive care, including dialysis as needed
Rationale: The treatment for diarrhea-associated HUS is primarily supportive, including dialysis if acute renal failure occurs. Antibiotics are not typically used as they may worsen the condition.
What is the first-line treatment for atypical HUS (aHUS) with antibodies to factor H?
A) Eculizumab
B) Plasma infusion or exchange
C) High-dose glucocorticoids
D) Rituximab
Answer: B) Plasma infusion or exchange
Rationale: Plasma infusion or exchange can be effective in aHUS when antibodies to factor H are present. However, it does not generally affect outcomes in other cases of aHUS.
Which of the following therapies has been shown to preserve renal function and improve outcomes in aHUS?
A) Glucocorticoids
B) Plasma exchange
C) Eculizumab
D) Rituximab
Answer: C) Eculizumab
Rationale: Eculizumab, a monoclonal antibody against complement C5, has shown efficacy in resolving aHUS and preserving renal function.
