A Young Woman With Abrupt Onset of Mucocutaneous Bleeding
Ronald N. Rubin, MD—Series Editor
Rubin RN. A young woman with abrupt onset of mucocutaneous bleeding. Consultant. 2018;58(10):279-280, 282.
A 32-year-old woman was referred by her dentist for evaluation of a possible bleeding disorder. She had been otherwise well but had begun to notice gum bleeding of unusual severity with brushing. She had gone to her dentist suspecting local periodontal causes. However, her dentist could detect no periodontal disease and noted easy bleeding induced by probing anywhere in the mouth, as well as the presence of several purpuric lesions under the tongue, and he advised her to promptly see her physician.
Additional history revealed that her last 2 menstrual periods had been somewhat heavier than normal and that in recent weeks, she had noted several bruises on her thighs that she had attributed to kicks from her 11-month-old son. She was taking no medication other than occasional acetaminophen as needed.
Results of a review of systems were negative, and she noted that to her knowledge, the results of her complete blood count (CBC) and chemistry/metabolic panels were normal less than a year ago at the time of her delivery.
She had delivered her son, as well as had wisdom tooth extraction and an appendectomy when younger, without any abnormal bleeding.
Physical examination findings were entirely unremarkable, save for several small purpuric lesions of the upper thighs, larger on the right than on the left, and small petechiae in her ankles.
Results of all routine laboratory tests—CBC and metabolic and chemistry panels—were normal, save for a strikingly low platelet count of 19,000/µL. No abnormal forms were reported to smear morphology.
Answer: C, the most likely diagnosis is adult immune thrombocytopenia, and an appropriate initial treatment regimen should be initiated.
The case presented here manifests a brief history of increased mucocutaneous bleeding in association with physical findings of petechiae and purpuric lesions, all consistent with problems related to platelets, either qualitative (defective function) or quantitative (platelet numbers too low). Sure enough, the wonderful, inexpensive, fast, and convenient CBC confirms a strikingly depressed platelet count of 19,000/µL. Although the initial evaluation is not entirely finished, her case appears to be an example of adult immune thrombocytopenia (which is also still referred to as idiopathic thrombocytopenic purpura, or ITP), likely the most commonly encountered bleeding disorder. This “What’s the ‘Take Home’?” article covers the clinical aspects of ITP—epidemiology, presentation, and diagnosis—while next month’s installment will address therapeutic considerations.
ITP is a common disorder with an incidence of 3 adults per 100,000 per year and a prevalence of 9.5 adults per 100,000.1 In my years of hematology practice, I estimate that I have seen well in excess of 500 cases, and I currently manage about 25 cases. There is a barbell epidemiology of patients younger than 30 (who are predominantly female, as in our case) and patients older than 65 (where the sex ratio is more even).1
Patients with ITP present in a variety of ways. The classic presentation is increased mucocutaneous bleeding (eg, gum bleeding with brushing, sporadic nosebleeds, menorrhagia, and the classical skin findings of pinpoint petechiae—usually in the ankle area—and larger purpura. The patient in our case manifested all of these. The thigh bruises were located in an area of minimal trauma, where her toddler’s feet kicked her when he was being carried. A platelet count in cases such as this will confirm the thrombocytopenia. When bleeding occurs such as seen here, the platelet count will almost always be below 50,000/µL and most often below 30,000/µL. The extent of mucocutaneous bleeding does correlate inversely with the platelet count. If the patient is using platelet-inhibiting drugs such as aspirin or nonsteroidal anti-inflammatory drugs, then bleeding may be seen more severely, even with platelet counts greater than 30,000 to 50,000/µL. In the current era of ubiquitous blood testing, another common presentation is a mild, incidentally found thrombocytopenia without signs or symptoms at all. And in fact, most patients who are eventually diagnosed with ITP do not present with purpura.1
Once thrombocytopenia is confirmed by CBC, a few exclusionary studies need to be performed, since ITP is a diagnosis of exclusion without a specific pathologic, genetic, or biochemical definitive diagnosis. The thrombocytopenia must be isolated without any other quantitative abnormality on CBC results (although iron deficiency anemia in a menstruating woman is an exception) or qualitative abnormality on a professionally reviewed peripheral blood smear—no abnormal red blood cells, white blood cells, or platelet forms.
A variety of consensus groups advise testing for hepatitis C virus and HIV infection, which can cause thrombocytopenia in otherwise as yet asymptomatic cases. A broad and extensive evaluation for secondary causes (eg, systemic lupus erythematosus and other autoimmune diseases) usually is not performed since the incidence is low (10%) and any primary triggering illness most often will be clinically obvious and/or demonstrate clues in the ITP evaluation process.1,2
Finally there is the issue of a bone marrow evaluation, once a “must” in the diagnosis, to identify the presence of megakaryocytes in the marrow in the face of peripheral blood thrombocytopenia. In stages, this strategy has changed such that marrow examination is no longer universally indicated and is no longer an immediate maneuver, even in situations where it has a role.1,2 In a major 2005 review, Cines and Bussel suggested reserving bone marrow examination for cases where otherwise typical patients were older than 60 years (as in rare cases of myelodysplasia presenting without anemia); for cases not showing good response to therapy (platelet count less than 50,000/µL); and prior to splenectomy if not previously obtained.2 More recent guidelines from the American Society of Hematology suggest that marrow biopsies essentially are not needed in any newly diagnosed patients.1 In either event, in the case presented here, Answer A is incorrect.
The pathophysiology of ITP has been more fully elucidated in recent years. Three mechanisms have now been demonstrated: platelet destruction by antiplatelet antibodies (originally demonstrated by Harrington and colleagues using self-experimentation in 1951),3 T-cell–mediated platelet destruction, and impaired megakaryocytopoiesis and thrombopoietin levels causing impaired production of platelets.1,4 The most common mechanism is antiplatelet immunoglobulin G antibodies, which are demonstrable in 60% to 70% of cases (yet are not sensitive nor specific enough to confirm ITP).1
Thus, the case and data presented here are most consistent with adult immune thrombocytopenia. Von Willebrand disease, a less common bleeding disorder most frequently diagnosed in women, is an inherited disorder in factor VIII synthesis and usually manifests at a younger age with menorrhagia or bleeding with tooth extraction, other surgery, or delivery. None of these were seen here, making Answer D far less likely and incorrect.
Answer B, treatment with platelet transfusion to attain and sustain 20,000/µL, introduces us to therapy considerations, which will be more completely addressed in next month’s column. The patient was not actively bleeding, save for mucocutaneous manifestations, and her platelet count is above 10,000/µL, so with almost any etiology of thrombocytopenia, urgent platelet transfusions are not indicated here, and other strategies to raise the platelet count and attempt more permanent resolution (Answer C) is the optimal choice.
Repeated CBC and careful manual examination of peripheral blood smears confirmed “isolated thrombocytopenia.” Serologies for hepatitis C and HIV were negative. A regimen of oral prednisone, 1 mg/kg, was initiated, and she will return for twice weekly monitoring of platelet count response. n
Ronald N. Rubin, MD, is a professor of medicine at the Lewis Katz School of Medicine at Temple University and is chief of clinical hematology in the Department of Medicine at Temple University Hospital in Philadelphia, Pennsylvania.
- Lampert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129(21):2829-2836.
- Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood. 2005;106(7):2244-2251.
- Harrington WJ, Minnich V, Hollingsworth JW, Moore CV. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med. 1951;38(1):1-10.
- Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood. 2009;113(26):6511-6521.