Pharmacology: Drug-Induced Thrombocytopenia

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Questions and Answers

What is the recommended treatment for patients with a neutrophil nadir of 50% reduction from baseline values?

Quinidine

G-CSF (Filgastrim) (correct)

Heparin

GM-CSF (Sargramostin) (correct)

What is the incidence of drug-associated thrombocytopenia?

1 case per 1,000,000 population

10 cases per 1,000,000 population (correct)

100 cases per 1,000,000 population

1,000 cases per 1,000,000 population

What is the definition of neutropenia in the context of drug-induced agranulocytosis?

A neutrophil count less than 1500/μl (correct)

A neutrophil count less than 2500/μl

A neutrophil count less than 1000/μl

A neutrophil count less than 2000/μl

Which of the following drugs is associated with an innocent bystander phenomenon in drug-induced agranulocytosis?

Quinidine Signup and view all the answers

Which of the following drugs is associated with a hapten-type immune reaction?

Vancomycin Signup and view all the answers

What is the leading cause of death among drug-induced hematologic disorders?

Aplastic anemia Signup and view all the answers

Which of the following is a characteristic of drug-induced hematologic disorders?

Can affect any cell line, including white blood cells, red blood cells, and platelets Signup and view all the answers

What is the approximate duration of neutrophil count recovery in drug-induced agranulocytosis?

4-24 days Signup and view all the answers

What is the typical time frame for recovery from drug-induced thrombocytopenia caused by quinidine?

1 week Signup and view all the answers

Which type of heparin-induced thrombocytopenia is more severe and immunologic?

Type II Signup and view all the answers

Which of the following antithyroid medications is associated with drug-induced agranulocytosis?

All of the above Signup and view all the answers

What is the risk of getting drug-induced hematologic disorders and the risk of death from DIHD associated with?

Increasing age Signup and view all the answers

What is the primary mechanism of antineoplastics in causing thrombocytopenia?

Direct toxicity Signup and view all the answers

Which of the following medications can cause drug-induced thrombocytopenia?

Heparin Signup and view all the answers

What is the primary treatment for drug-induced agranulocytosis?

Removal of the offending drug Signup and view all the answers

What is the term for the failure of the bone marrow to produce blood cells, leading to a decrease in the number of red and white blood cells and platelets?

Aplastic anemia Signup and view all the answers

What is the name of the type of reaction that occurs with penicillin in drug-induced agranulocytosis?

Hapten-type reaction Signup and view all the answers

What is the characteristic of Type I heparin-induced thrombocytopenia?

Non-immunologic response, mild, reversible Signup and view all the answers

What is the approximate percentage of drug-induced agranulocytosis cases attributed to antithyroid medications?

7-23% Signup and view all the answers

Which of the following is a risk factor for developing heparin-induced thrombocytopenia?

Patients who had recent major surgery Signup and view all the answers

Which of the following is a type of drug-induced hematologic disorder that occurs when the bone marrow fails to produce enough white blood cells?

Agranulocytosis Signup and view all the answers

What is the purpose of colony-stimulating factors in the treatment of drug-induced agranulocytosis?

To promote neutrophil recovery Signup and view all the answers

Which of the following medications can cause antithyroid side effects, leading to a decrease in the production of white blood cells?

Antithyroid medication Signup and view all the answers

What is the term for a type of medication that can stimulate the production of white blood cells, red blood cells, or platelets?

Colony-stimulating factors Signup and view all the answers

Study Notes

Drug-Induced Thrombocytopenia

Incidence: 10 cases per 1,000,000 population
Symptoms:
- Early phase: increased bruising, petechiae, ecchymoses, and epistaxis
- Later phase: bleeding of mucous membrane and purpura
Examples of drugs and their mechanisms:
- Immunologic reactions:
  - Quinidine, sulfonamides, rifampin, heparin
  - Vancomycin, penicillin, cephalosporin - Hapten-type immune reaction
  - Gold compounds, procainamide– platelet specific antibody
- Antineoplastics – direct toxicity reaction
- Heparin – Type I & Type II

Heparin-Induced Thrombocytopenia

Type I:
- Non-immunologic response, mild, reversible
- Occurs in 10-20% of patients on heparin
- Platelet count slowly returns to baseline
- Usually asymptomatic
Type II:
- Immunologic response, more severe
- Less common (1 to 5% for heparin, 0.8% for LMWH)
- Platelet count generally begins to decline 5 to 10 days after the start
- Risk factors: patients who had recent major surgery

Drug-Induced Hematological Disorders (DIHD)

Goal:
- To discuss the various types of DIHD
- To recommend the appropriate laboratory analysis, diagnostic assessment, and management in DIHD
- To propose appropriate pharmacotherapy plans based on the different types of DIHD

Case Study

A 45-year-old lady presented to the clinic complaining of weakness, fatigue, and shortness of breath
She reports easy bruising and petechiae on her skin
She is a known case of T2DM and HPT, and is currently on Amlodipine 10 mg OD and Metformin 500 mg BD

General Information

Some agents cause predictable hematologic disease (e.g., antineoplastics), but others induce idiosyncratic reactions not directly related to the drugs’ pharmacology
Associated with significant drug-related morbidity and mortality
Aplastic anemia was the leading cause of death, followed by thrombocytopenia, agranulocytosis, and hemolytic anemia
The risk of getting DIHD and the risk of death from DIHD is higher with increasing age

Types of DIHD

Drug-induced agranulocytosis
Drug-induced thrombocytopaenia
Drug-induced haemolytic anaemia
- DI immune haemolytic anaemia
- DI oxidative haemolytic anaemia
Drug-induced megaloblastic anaemia
Drug-induced aplastic anaemia

Drug-Induced Agranulocytosis

Definition:
- Leucopenia: TWBC less than 3000/μl
- Neutropenia: neutrophil count less than 1500/μl
- Granulocytopenia: Granulocyte count less than 1500/μl (includes eosinophil & basophil)
- Agranulocytosis: (severe neutropenia) a reduction in the number of mature myeloid cells in the blood (granulocytes and immature granulocytes [bands]) to a total count of 500 cells/mm3 or less
Examples of drugs and their mechanisms:
- Penicillin – hapten-type reaction
- Quinidine, phenothiazine – innocent bystander phenomenon
- High dose B-lactam antibiotics, carbamazepine, valproic acid – autoimmune reaction
- Clozapine, ticlopidine – direct toxicity to progenitor stem cells
Symptoms:
- Sore throat, fever, malaise, weakness, chills
Duration: Can appear within days to weeks after initiation of therapy
Treatment:
- Removal of offending drug
- Symptomatic treatment (e.g., Abx for infection)
- Colony-stimulating factors (e.g., GM-CSF, G-CSF)

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Description

This quiz covers the effects of certain medications, such as GM-CSF and G-CSF, on blood platelet count, including symptoms and incidence rates. It's a crucial topic for pharmacology and medical students.