A SELF-TEST IM BOARD REVIEW DAVID L. LONGWORTH, MD, JAMES K STOLLER, MD, EDITORS OF CLINICAL PETER MAZZONE, MD CRAIG NIELSEN, MD RECOGNITION Department of General Internal Medicine, Department of General Internal Medicine, 1 Cleveland Clinic. Cleveland Clinic. A 61-year-old woman with thrombocytopenia and a rash 61-YEAR-OLD WOMAN with a history of rate 20. She was not in acute distress. 0seizures was transferred to our facility Examination of her skin revealed confluent from another hospital for further evaluation macular purpuric lesions involving the entire and management of a rash and a low platelet body and face, with relative sparing of the count. palms and soles. Purpuric papules were also The woman was initially admitted to the found on the back of her hands and legs. other hospital 4 weeks earlier due to the onset There was also conjunctival injection with of focal seizures. An extensive evaluation periorbital edema, but mucous membranes revealed no etiology for the seizures. She was were clear. The chest was normal on ausculta- discharged home with her seizures well con- tion, and no wheezes were heard. Her cardiac trolled with phenytoin. Approximately 3 examination was normal. There was no weeks later, she noticed a diffuse rash without detectable organomegaly, and a stool test for any other associated symptoms. Her primary occult blood was positive. She had strong physician discontinued the phenytoin and peripheral pulses with no edema. substituted carbamazepine. Two days later she felt that her rash had worsened, and she • LABORATORY RESULTS AT ADMISSION became frustrated and stopped taking all of Platelet her medications. She presented to the emer- Laboratory results at the time of her admission destruction gency department 2 days later with diarrhea, to our facility are listed in TABLE 1. Her white polyuria, and polydypsia. At that time a blood blood cell count was 21.4 x 10y/L (54% neu- can be due to workup revealed a plasma glucose level of 824 trophils, 19% lymphocytes, and 15% immune or mg/dL and a platelet count of 10 x 109/L. She eosinophils), with a hemoglobin (Hgb) of was admitted to the hospital and was later 11.8 g/dL and a platelet count of 5 x 10y/L. nonimmune transferred to our facility. Results of coagulation studies were normal. processes Medical history. A review of her medical A peripheral blood smear was immediately history showed type 2 diabetes requiring reviewed, showing leukocytosis with immature insulin; asthma; and the focal seizures men- neutrophils (ie, left shift), eosinophils, and tioned above. Current and recent medications decreased platelets. There was no evidence of included NPH insulin 40 U every morning red cell fragments, target cells, or schistocytes. and 20 U every evening; carbamazepine (stopped 2 days prior to transfer); phenytoin LOW PLATELET COUNT (stopped 9 days prior to being transferred to our facility); and albuterol and ipratropium This patient's low platelet count might bromide inhalers. Her only known drug aller- 1 result from each of the following, except gy was to glipizide. She did not smoke or drink which one? alcohol. Physical findings. On physical examina- • Drug effect tion, she appeared comfortable. Her tempera- • Pseudothrombocytopenia ture was 37.2°C, heart rate 100 bpm (regular), • Immune platelet destruction blood pressure 142/84 mm Hg, and respiratory • Nonimmune platelet destruction CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 65 • NUMBER 4 APRIL 1998 209 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. THROMBOCYTOPENIA MAZZONE AND NIELSEN TABLE 1 Decreased production of platelets can be Laboratory test results caused by an insult to the hematopoietic cells (eg, from cytotoxic therapy, drugs, toxins, at the time of hospital admission infections, aplasia) or replacement of other- STUDY VALUE NORMAL RANGE wise normal marrow (eg, as in infiltration of the marrow by malignant cells, myelofibrosis). Sodium 124 mmol/L 132-146 Platelet sequestration is usually due to Potassium 4.5 mmol/L 3.5-5.0 functional hypersplenism (eg, as in cirrhosis, passive congestion, malignancy, infections). Chloride 94 mmol/L 98-110 Platelet destruction can be due to Carbon dioxide 23 mmol/L 24-32 immune or nonimmune processes. Immune Blood urea nitrogen 46 mg/dL 8-25 causes include idiopathic thrombocytopenic Creatinine 1.5 mg/dL 0.7-1.4 purpura, transfusion-related alloimmune Glucose 685 mg/dL 65-110 thrombocytopenia, and drugs. Nonimmune Bilirubin 1.4 mg/dL 0-1.5 processes include disseminated intravascular coagulation, thrombotic thrombocytopenic Lactate dehydrogenase (LDH) 685 U/L 100-220 purpura, sepsis, mechanical destruction, and Alkaline phosphatase 340 U/L 20-120 again, drugs. Aspartate aminotransferase (AST) 35 U/L 7-40 Hemoglobin 11.8 g/dL 12-16 • THE INITIAL HOSPITAL COURSE White blood cells 21.4 x 109/L 4.0-11.0 Neutrophils 54% 40-70 On admission to oar hospital, the patient underwent hydration with normal saline and Lymphocytes 19 % 15-45 received insulin intravenously. Phenobarbital Eosinophils 15 % 1-6 was substituted for her prescription for carba- Platelets 5 x 109/L 150-400 mazepine. Red blood cells 4.05 x 1012/L 4.2-5.4 A hematology consultation was obtained. Bone marrow aspiration was performed, and microscopic examination of the aspirate revealed a cellular marrow with megakary- Investigating a low platelet count requires an ocytes. These findings suggested a peripheral organized approach, making efficient and loss of platelets. The clinical picture and the accurate use of available diagnostic tests and results of bone marrow analysis were felt to be treatments. consistent with idiopathic thrombocytopenic First, one must determine if the low purpura. Treatment with intravenous platelet count signifies true thrombocytopenia immunoglobulin and two units of platelets was or pseudothrombocytopenia. Pseudothrom- started. bocytopenia occurs when platelets clump in Over the next 2 days the patient com- an EDTA anticoagulated tube. Platelet clumps plained of a sore throat and was noted to have are seen on the peripheral smear, and a normal a temperature of 38.3°C. She was drowsy. platelet count is obtained from a heparinized Several laboratory values during this time tube. were notable: the Hgb fell from 11.8 g/dL to Our patient's peripheral smear revealed a 10.0 g/dL, then 8.9 g/dL. The platelet count decreased number of platelets without platelet remained below 10 x 109/L (6 x 109/L). clumping. Thus, it appears that she had true Her lactate dehydrogenase (LDH) thrombocytopenia, making pseudothrombo- increased to 1844 U/L, bilirubin to 2.4 mg/dL, cytopenia the correct choice above. and AST to 105 U/L. Alkaline phosphatase decreased to 263 U/L. A dipstick urinalysis Causes of thrombocytopenia found 3+ Hgb and no bilirubin. A microscop- Thrombocytopenia can be secondary to ic examination of the urine found more than decreased production of platelets, sequestration 25 red blood cells and 11 to 25 white blood of platelets, or destruction of platelets (TABLE 2). cells per high-powered field. 210 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 65 • NUMBER 4 APRIL 1998 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. HEMOLYSIS TABLE 2 Differential diagnosis of A decreasing level of which of the follow- thrombocytopenia by cause ing would provide evidence that hemoly- sis is occurring Caused by decreased platelet production Hematopoietic cell insult • Urine hemosiderin Cytotoxic therapy • LDH Drugs • Methemalbumin Toxins • Haptoglobin Infections Aplasia Several of the above laboratory results suggest Bone marrow replacement hemolysis. When evaluating a patient for Malignant cells hemolysis, several tests should be considered. Myelofibrosis During hemolysis, the reticulocyte count increases to compensate for the falling Hgh Caused by platelet sequestration level. LDH and bilirubin are released and thus Functional hypersplenism elevated, whereas the haptoglobin and hemo- Cirrhosis pexin levels fall as they bind to free hemoglo- Passive splenic congestion bin and are quickly cleared in the liver. Free Malignancy hemoglobin is oxidized to methemoglobin, Infection which subsequently splits from the globin por- Caused by platelet destruction tion and binds to free albumin, causing a rise Immune processes in methemalbumin levels. The heme tetramer Idiopathic thrombocytopenic purpura splits to a dimer, is filtered in the kidney, and Transfusion related is absorbed by the renal tubules, where the Drugs iron is stored as hemosiderin. As the tubular Nonimmune processes cells die, they slough into the urine, leading to Disseminated intravascular coagulation an elevated urine hemosiderin level. Thrombotic thrombocytopenic purpura During Thus, erf the choices above, haptoglobin is Sepsis hemolysis, the only one that decreases during hemolysis. Mechanical destruction Drugs the • ANALYZING THE CAUSES OF HEMOLYSIS reticulocyte There are several ways to organize the causes count rises to of hemolysis. One way is to divide the causes counter the into intrinsic red blood cell abnormalities and Review of our patient's subjective and abnormalities not intrinsic to red blood cells objective problems revealed the characteristic falling Hgb (TABLE 3). pentad of thrombotic thrombocytopenic pur- Intrinsic abnormalities can be congenital, pura (see below). such as membrane defects (eg, spherocytosis, elliptocytosis) and enzymopathies (eg, glucose- • THROMBOTIC THROMBOCYTOPENIC