Patients on daily drug regimens require occasional CBC test reports
Editors:
- Dr. Praful B. Godkar (Ph.D)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD. - Dr. Gauri Kulkarni MD (Pathology)
Vice President, AGD Biomedicals (Pvt) LTD.
Patients on daily drug-regimens may lead to drug-induced thrombocytopenia (DIT)(1-3). DIT may take place when certain medicines interfere with the ability of the body to generate normal levels of platelets or destroy platelets by their specific actions(1). Thrombocytopenia is a serious disorder that may cause severe bleeding, including internal hemorrhage or hemorrhagic stroke, which can be fatal(2,8). Thrombocytopenia may also elevate the risk of thrombus formation within the systemic circulation. Thrombocytopenia is the common coagulation disorder in patients admitted in intensive care wards of a hospital(1). Thrombocytopenia often has no symptoms and can be quickly diagnosed by complete blood count test performed on a hematology analyzer based on cutting-age technology such as the AGD HT-340 and backed by AGD C-102 coagulometer (8).
NOTE(8)
(1) Normal range of platelet count is 1,50,000 to 4,50,000 per microliter blood. Platelet count below (50,000/microliter) increases the risk of bleeding. A platelet count below 20,000 per microliter is a medical emergency, since, it signifies a high risk of spontaneous bleeding. A platelet count below 10,000 can lead to central nervous system hemorrhage.
(2) Thrombocytopenia usually first appears as 1–2 mm red petechiae on the skin, which can merge and form purple-blue ecchymoses.
(3) A physical examination shows bleeding, petechiae or ecchymoses, and ongoing bleeding from injuries or wounds.
(4) Complete medical history is very important to ensure that the low platelet count is not secondary to another disorder.
Q1. What are the various drugs that may lead to thrombocytopenia?
ANS(1): The following are some examples of drugs that may cause thrombocytopenia:
Examples: Heparin (blood thinner), penicillin (antibiotic), quinine (antimalarial), quinidine (malaria), sulfonamides(antibiotic), valproic acid (anticonvulsant), Chemotherapy medicines (treatment on cancer), furosemide (hypertension), nonsteroidal anti-inflammatory drugs (NSAIDs, pain killers), ranitidine (antiacid), linezolid (antibiotic), statins (cholesterol lowering), sulphonylureas (Example: Tolbutamide, Gliclazide, glimepiride and glipizide, etc, Oral drugs on diabetes treatment) etc.
NOTE(8)
(A) There are two types of drug-induced thrombocytopenia: Drug-induced immune thrombocytopenia and drug-induced nonimmune thrombocytopenia.
(B) In the case of drug-induced immune thrombocytopenia a drug causes the immune system to produce antibodies against platelets, which destroy them.
(C) In the case of drug-induced nonimmune thrombocytopenia a drug prevents bone marrow to produce sufficient platelets.
Q2. What are the general symptoms related to thrombocytopenia?
ANS: Easy bruising, abnormal bleeding, bleeding from teeth, petechiae on the skin (pinpoint red spots).
Q3. What is the treatment to stop abnormal bleeding?
ANS: The first line of treatment is to stop abnormal bleeding is to discontinue the use of the medicine that is causing abnormal bleeding and get a prompt CBC report with coagulation panel test report.
Q4. What are coagulation panel tests?
ANS: Prothrombin Time (PT), Activated partial thromboplastin time (aPTT), Thrombin time ( TT) and D-Dimer.
CASE STUDY
During a routine blood examination, the following is a CBC report of a 65-year-old diabetic man, who was under oral diabetic drug-therapy (Combination of: Glipizide, Metformin, Dapagliflozin).
COMPLETE BLOOD COUNT
| PARAMETER | RESULT | NORMAL RANGE |
| Hemoglobin | 13.8 g/dl | 13–18 g/dl |
| Total erythrocyte count | 5.8 X 1012 /l | 5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 8.5 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count | ||
| Neutrophils | 70% | 40–75% |
| Lymphocytes | 38% | 20–45 % |
| Eosinophils | 1% | 1–4 % |
| Monocytes | 1% | 2–8 % |
| PCV | 42% | 36–48% |
| MCV | 86 fL | 82–92 fL |
| MCH | 30 pg | 27–32 pg |
| MCHC | 30% | 32–36 % |
| RDW-CV | 16.0 | 12–14 |
| Platelet count | 38 X 109/l | 150–400 X 109/l |
| Mentzer Index (MI) | 14.82 | > 13 |
STAINED BLOOD SMEAR
Microscopic examination observations:
Abnormal blood cells were not detected.
INTERPRETATION
Drug-induced thrombocytopenia, since blood platelet count is very low and patient is on oral-hypoglycemic drug combinations, which contain one drug related to Sulfonylurea type(4-7).
NOTE
(A) Incidences of sulfonylureas leading to thrombocytopenia are extremely rare (average 38 cases per million users).
(B) Drug-induced thrombocytopenia is usually reversible by the discontinuation of the drug and replacement with another type of oral hypoglycemic drug.
(C) Physicians usually advise patients to monitor platelet counts after initiating treatment with sulfonylureas, and any episodes of unexplained bruising or bleeding.
(D) The patient was on oral hypoglycemic drugs, a combination containing, Glipizide: (a second generation sulfonylurea drug), metformin (Biguanidine) and Farxiga (Dapaglifloxin).
(E) Sulfonylureas drugs can cause thrombocytopenia mainly through a drug-induced immune reaction that leads to immune-mediated destruction of platelets(4-7).
(F) Sulfonylureas increase insulin secretion, Biguanides increase insulin sensitivity and Farxiga decrease renal tubular reabsorption of glucose. Thus, this combination of drugs with appropriate amounts maintains normal glycemic control, in the treatment of Type 2 Diabetes mellitus(8).
(G) All first to third generation sulfonylurea drugs have a similar drug-induced immune reaction that may lead to destruction of platelets only in some diabetic patients (4-7).
References
(1) Marini JJ, Dries DJ (2019). Critical care medicine: the essentials and more. Philadelphia: Wolters Kluwer. ISBN 978-1-4963-0291-5. OCLC 1060947164.
(2) “Platelet count”. MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. Archived from the original on 2015-04-05. Retrieved 2015-05-01.
(3) “What Is Thrombocytopenia?”. National Heart, Lung, and Blood Institute (NHLBI). U.S. Department of Health and Human Services. Archived from the original on 2015-05-18. Retrieved 2015-05-01.
(4) Gliclazide induced thrombocytopenia. Y. Aydin1, N. Direktör2, D. Berker2, E. Onder1, A. Gungor1, G. Celbek1. Case Report doi:10.4183./aeb.2009.533.
(5) Israeli A, Matzner Y, Or R, Raz I. Glipalamide causing thrombocytopenia and bleeding tendency: case reports and review of the literature. Klin Wochenschr 1988; 66:223-224.
(6). Grace WJ. Thrombocytopenia in a patient taking chlorpropamide. N Engl J Med 1959; 260:711-712.
(7) Cartron G, Jonville-Bera AP, Autret-Leca E, Colombat P. Glimepiride-induced thrombocytopenic purpura. The Annals of Pharmacotherapy 2000; 34:120.
(8) Traumann KJ, Grom E, Schwartzkopf H. Pancytopenia in diabetes mellitus treatment with tolbutamide? Dtsch Med Wochenschr 1975; 100(6):250-251.
(9) Godkar PB, Godkar DP. Textbook of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.
