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PubMed1975

Intensive leukapheresis as initial therapy for chronic granulocytic leukemia.

Intensive leukapheresis has been used as the initial treatment of chronic granulocytic leukemia (CGL) in six patients. The number of leukaphereses ranged from 3 in 7 days to 13 in 39 days (mean, 8 in 22 days). The procedures were well tolerated, and in all patients there was improvement in hematologic values, in most cases with considerable reduction in the peripheral leukocytosis and thrombocytosis and in the proportion of immature granulocytic cells in the circulation. Splenomegaly decreased considerably in the four patients who had more than four leukaphereses. Symptoms of sweating, malaise, and pain due to splenomegaly were rapidly relieved. Problems due to hyperuricemia did not occur, but four patients required blood transfusions for correction of anemia. This method of initial treatment of CGL appears to give more rapid relief of symptoms than does conventional chemotherapy; it incurs no risk of hyperuricemia and lessens that associated with thrombocytosis. In addition, large quantities of granulocyte-rich plasma are made available for the treatment of infections in neutropenic patients. Intensive leukapheresis deserves more widespread evaluation as the initial treatment of CGL.

Adolescent↗
PubMed2000

[Coagulation disorders in cancer patients: possible opportunity for therapy].

Coagulation disorders occur often in cancer patients. Thrombosis or embolism may be the first sign of an underlying malignancy. In addition, subclinical coagulation disturbances have been found in the blood of cancer patients, for example elevated concentrations of tissue factor or thrombin-antithrombin complexes. In 20% of the patients thrombocytosis occurs, and for lung and colon cancer it was found that thrombocytosis is an independent negative prognostic factor for survival. The role of an activated coagulation cascade in tumour growth is not completely clear, but there is strong evidence that the formation of a temporary fibrin matrix stimulates the formation of new blood vessels (angiogenesis) and supports tumour growth and metastasis formation. Preclinical investigations demonstrated that tumour growth and metastasis formation can be inhibited by anticoagulants. Clinical studies suggest a beneficial effect of anticoagulants on the survival of cancer patients, but phase III randomised clinical trials should be performed to determine the effect of longterm administration of anticoagulants.

Anticoagulants↗
PubMed2000

Diagnosis of essential thrombocythemia at platelet counts between 400 and 600x10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC).

BACKGROUND AND OBJECTIVE: Diagnostic criteria for essential thrombocythemia (ET) remain essentially negative, that is, exclusion of other myeloproliferative diseases and causes of reactive thrombocytosis. A platelet count above 600x10(9)/L is still generally considered an absolute diagnostic criterion although new protocols for positive diagnostic criteria have recently been proposed, reducing the stringency of a definite platelet limit. This study demonstrates that a platelet count 600x10(9)/L is not a reliable diagnostic criterion for ET, especially in the early stages. DESIGN AND METHODS: An ongoing retrospective study by the GIMMC analyzed 2,316 ET patients diagnosed between 1986 and 1995. Of these 2,316 patients, diagnosed according to the PVSG criteria, 68 had a platelet count 600x10(9)/L and were analyzed separately; 37 out of 68 were excluded from this analysis because of a follow-up shorter than 2 years and/or because of treatment with myelosuppressive agents. The remaining 31 patients were the subjects of our study. RESULTS: After a median follow-up of 4.56 years (range 2-9.6 years) none of the 31 patients had a spontaneous decrease of platelets to the normal range. Transformation to a different chronic myeloproliferative disorders was never observed and no patient developed a condition known to produce reactive thrombocytosis. During follow-up, 23 patients (74%) were treated with anti-aggregating drugs, mainly aspirin. The disease did not evolve into acute leukemia in any patient, 1 had a thrombotic event and none presented hemorrhagic episodes. Median platelet count during follow-up was 534x10(9)/L (range 398-997x10(9)/L). INTERPRETATION AND CONCLUSIONS: Long term follow-up has documented that our 31 patients were correctly diagnosed as having ET, although platelet count was 600x10(9)/L. Our patients were probably in a early phase of their disease and following updated PVSG criteria would have been misdiagnosed leading to incomplete recognition of the natural history of the disease. Further, because an early diagnosis could also have a clinical relevance, our results outline the need for new criteria for the diagnosis of ET. The exclusion of patients with a platelet count between 400 and 600x10(9)/L may prevent patients, nevertheless at risk of vascular complications, from being treated.

Adolescent↗
PubMed2000

Stimulation of megakaryocytopoiesis and platelet production during growth of an experimental lymphoma.

The effect of malignant tumor growth on host's megakaryocytopoiesis and platelet production was studied in mice bearing transplantable Dalton's lymphoma. Tumor growth was paralleled by thrombocytosis, neutrophilia, and anemia. Platelet 51Cr half-life was normal but incorporation of 75Selenomethionine into circulating platelets was significantly enhanced in the tumor bearers suggesting stimulated thrombopoiesis while platelet life span remained unchanged. Megakaryocytes and their precursors, the small acetyl cholinesterase positive cells, were found in increased numbers in the bone marrow (BM) and particularly in the spleen where five to eight-fold rise was observed at the log phase of tumor growth. In addition, a remarkable increase in the number of megakaryocyte progenitors (CFU-MK and MK CFU-S) was observed both in the BM and spleen. Stimulation of these progenitors was more pronounced in the spleen than in the marrow, and the change was noticeable even from the third day of tumor bearing. Therefore, the results suggest that thrombocytosis associated with the growth of this experimental lymphoma was due to accelerated platelet production following stimulated megakaryocytopoiesis especially in the spleen.

Acetylcholinesterase↗
PubMed2000

Myeloproliferative Disease: Markers of Endothelial and Platelet Status in Patients with Essential Thrombocythemia and Polycythemia Vera.

Vascular complications are the main cause of morbidity in polycythemia vera (PV) and essential thrombocythemia (ET). To investigate plasma concentrations of soluble P-selectin (sP-Sel.), soluble E-selectin (sE-Sel.) and soluble thrombomodulin (sTM) in relation to the presence of thromboembolic events 38 patients with Chronic Myeloproliferative Disorders (CMD) (14 PV pts and 24 ET pts), 15 age - matched controls and 15 patients with secondary thrombocytosis were studied. Plasma levels of P-Sel., E-Sel. and TM were significantly increased in the group of patients as compared with control subjects (respectively p < 0.001, p < 0.04 and p < 0.01). sP-Sel. levels showed no significant difference between the patients and those with secondary thrombocytosis. No difference in sP-sel levels were also observed between subgroups of CMD patients with and without vascular complications. However, among patients with ET, those with thrombosis had higher sP-Sel levels than those without thrombosis (1.177 +/- 110.48 ng/ml vs 816.25 +/- 99.27 ng/ml). High levels of sE-Sel and sTM were found in CMD patients (71.93 +/- 39.08 ng/ml and 35.81 +/- 20.79 ng/ml, respectively). Plasma sE-Sel. concentration was significantly higher in CMD patients with thrombosis than that in CMD patients without thrombosis (p < 0.001). There was no difference in sTM concentration between two groups. These findings indicate that sustained endothelium and platelet activation is present in patients with ET and PV and it might contribute to the pathogenesis of thromboembolic events in these patients.

Journal Article↗
PubMed2002

Hemostatic changes in active pulmonary tuberculosis.

OBJECTIVE: Severe pulmonary tuberculosis (PTB) is sometimes complicated by deep vein thrombosis (DVT). We have searched for possible hemostatic disturbances that are predisposing factors for venous thrombosis in patients with PTB. DESIGN: Coagulation and platelet function tests were studied in 45 patients with active PTB and 20 healthy control volunteers before therapy. Findings were compared with results at 30 days. RESULTS: Analysis in patients with active PTB showed anemia, leucocytosis, thrombocytosis, elevation in plasma fibrinogen, factor VIII, plasminogen activator inhibitor 1 (PAI-1) with depressed antithrombin III (AT III) and protein C (PC) levels. On the 30th day of treatment, anemia, leucocytosis and thrombocytosis were improved. Fibrinogen and factor VIII levels had decreased to normal levels, PC and AT III levels had increased to normal levels, and there was no difference in PAI-1 levels. We found no activated protein C resistance. Platelet aggregation studies demonstrated increased platelet activation. However, DVT was not detected in patients during the follow-up period. CONCLUSION: Decreased AT III, PC and elevated plasma fibrinogen levels and increased platelet aggregation appear to induce a hypercoagulable state seen in PTB and improve with treatment.

Adult↗
PubMedDate not supplied

Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients.

BACKGROUND: Many factors have prognostic significance in lung cancer. However, their practical value remains controversial except for stage of disease, performance status, and, perhaps, weight loss. METHODS: In the present study, counts of platelet (P), leukocyte (L), neutrophil (N), and hemoglobin serum content (Hb) were analyzed in 1201 new consecutive lung cancer patients. A set of 28 anthropometric, clinical, physical, laboratory, radiological, and pathological variables was prospectively recorded for all patients. Patients were carefully followed-up, and their subsequent clinical course recorded. RESULTS: Anemia, leukocytosis, and thrombocytosis were present in 56%, 32%, and 17% of patients, respectively. Correlation tests showed that P was significantly correlated with L, N and Hb (rs = 0.353, 0.352, and -0.295, respectively). Other significant associations were those between Hb and Karnofsky Performance Status (KPS) (rs = 0.232), weight loss (rs = -0.210), and serum protein (rs = 0.263). N and L were correlated with KPS (rs = -0.217 and -0.186), stage of disease (rs = 0.153 and 0.135) and number of metastasis (rs = 0.121 and 0.109). Univariate analyses of survival showed that: a) abnormal values of L were prognosticantly significant in adenocarcinoma (p < 0.0001); b) patients with Hb < 13 g/dL had significantly shorter survivals (p = 0.0002); and c) thrombocytosis was associated to a poor outcome in patients with adenocarcinoma and epidermoid cancers (p = 0.0061 and 0.0072, respectively). The multivariate model selected, in decreasing order of significance, the following variables: 1) stage of disease; 2) KPS; 3) neutrophils; 4) age; and 5) sex. CONCLUSION: This data indicates that only the leukocyte counts is an independent prognostic factors of survival in lung cancer.

Adenocarcinoma↗
PubMedDate not supplied

Atypical Kawasaki disease: report of two cases.

Two cases of atypical Kawasaki disease are reported. Case 1 was a five-month-old male infant admitted to this hospital with a 10-day's history of high fever. On examination, he appeared ill-looking and only hepatomegaly was noted. Laboratory studies showed leukocytosis, thrombocytosis, elevated ESR and pleocytosis in CSF. He was treated as sepsis with meningitis. Sudden death occurred on the eighth day of admission, and left coronary artery aneurysm with thrombosis was noted at autopsy. Case 2 was a four-month-old male infant referred to our hospital with fever and cervical lymphadenopathy of 11 day's duration, and unresponsive to antibiotics. Skin rash had developed after oxacillin injection. Echocardiogram, performed on the third day of admission, disclosed a 5-8 mm aneurysm of the left coronary artery and a 4 mm aneurysm of the right coronary artery. Before a specific diagnostic test for Kawasaki disease becomes available, we suggest that a possible diagnosis of Kawasaki disease and echocardiographic evaluation should be considered in case of (1) presence of partial criteria of Kawasaki disease with thrombocytosis; and/or (2) young infants with prolonged unexplained fever.

Echocardiography↗
PubMed2004

A long-term study of young patients with essential thrombocythemia treated with anagrelide.

BACKGROUND AND OBJECTIVES: Essential thrombocythemia (ET) can be complicated by life-threatening thrombosis and has a risk of converting into acute leukemia. Cytoreductive therapy may reduce the risk of thromboembolic complications. Herein, we report the results of a long-term study of patients with ET treated with anagrelide to control thrombocytosis. DESIGN AND METHODS: Thirty-nine (34 evaluable) patients (median age, 33 years; 24 previously untreated) were enrolled between 1989-1996; the mean platelet count prior to therapy was 1197x10(9)/L. Only 9 out of 34 evaluable patients were at high risk of thrombosis (platelet count more than 1500x10(9)/L). The initial dose of anagrelide (0.5 mg/bid for 7 days) was increased by 0.5 mg/day (maximum dose: 3 mg/day) until a response was seen. RESULTS: A complete response (platelets < 450x10(9)/L for >1 month) was seen in 15 /34 (44%) patients and a partial response (platelets 450-600x10(9)/L for >1 month) was seen in 17/34 ( 50%), so that the some kind of response was seen in 32/34 (94%) of the patients at a median time of 4.2 months after starting treatment. Seventeen patients (50%) are still being treated and have achieved platelet control for a maximum follow-up of 12.5 years. Late onset anemia occurred in 4/39 patients. Three out of 39 patients (8%) had cardiac disorders. INTERPRETATION AND CONCLUSIONS: Anagrelide appears suitable for controlling thrombocytosis in ET patients over the long-term. This drug may be used in patients younger than 60 years, with the exclusion of women of child-bearing potential and subjects aged 40-60 years with a history of major thrombotic events. Anagrelide should not be administered to patients with cardiac disorders, and a careful approach to patients should include monitoring of heart function before and during treatment.

Adult↗
PubMed2005

Progenitor cell trafficking in physiologic conditions and in myeloproliferative diseases: quantification of CD34+ cells by polymerase chain reaction.

BACKGROUND AND OBJECTIVES: Previous studies using flow cytometry have shown that CD34+ cell trafficking is increased in patients with chronic idiopathic myelofibrosis. Few data exist on physiologic CD34 + cell trafficking and the quantification of very low cell ranges requires reliable and sensitive measurement techniques. The aim of this study was to establish a quantitative polymerase chain reaction (PCR) technique for studying CD34+ cell trafficking in physiologic conditions, and in patients with myeloproliferative diseases. DESIGN AND METHODS: CD34+ cell trafficking was measured in 56 controls [(healthy controls (n=21), patients with ischemic cardiopathy (n=21), patients with secondary thrombocytosis or erythrocytosis (n=14)], and in 37 untreated patients with myeloproliferative diseases diagnosed according to the WHO-criteria [(essential thrombocythemia (n=10), polycythemia vera (n=14) and chronic idiopathic myelofibrosis (n=13)]. Quantitative PCR was used to determine CD34 mRNA expression in peripheral blood samples. RESULTS: Physiologic CD34 mRNA expression ranges were determined in the healthy control group. Mean CD34 mRNA expression was within the physiologic range in patients with ischemic cardiopathy, secondary thrombocytosis or erythrocytosis, essential thrombocythemia and polycythemia vera (p=0.146), but was significantly increased in patients with chronic idiopathic myelofibrosis (p<0.001). When analyzed individually, 12/13 patients with chronic idiopathic myelofibrosis and 3/14 patients with polycythemia vera showed CD34 mRNA expression above the physiologic range. INTERPRETATION AND CONCLUSIONS: This is a first report about CD34+ cell trafficking measured by quantitative PCR. Quantitative PCR is a reliable method suitable for the quantification of very low cell populations. Our study confirms the significant increase of CD34+ cell trafficking in patients with chronic idiopathic myelofibrosis, and in a subset of patients with polycythemia vera. Prospective studies are underway to characterize these circulating CD34+ cells and to investigate their role in the pathophysiology of myeloproliferative diseases.

Adult↗
PubMed2005

Difficult-to-treat nephrotic syndrome: management and outcome.

A retrospective study was performed in 68 patients diagnosed as having idiopathic nephrotic syndrome with steroid-dependent, steroid-resistant or frequent relapse subtypes at the Department of Pediatrics, Siriraj Hospital during Jan 1996-Dec 2004. Male to female ratio was 3.3:1 and mean age (+/- SD) was 8.4 +/- 3.5 years. Mean follow up time (+/- SD) was 47.4 +/- 30.5 months. Renal biopsy was done in 60 patients, showing IgM nephropathy in 73.3%. Fifty-four patients (79.4%) received cyclophosphamide at a dose (+/- SD) of 2.2 +/- 0.5 mg/kg/d for 11.6 +/- 3.4 weeks. Negative proteinuria at 1 year was found in 70% and prednisolone was discontinued in 52%. Leucopenia was found in 9.2%. At last follow up, 34% of the patients were still in remission. Enalapril was prescribed in 50 patients for 12.4 +/- 10.0 months. Thirty-six patients also received cyclophosphamide. Remission at 1 year was achieved in 66% and prednisolone discontinued in 28%. Twelve patients (24%) were still in remission at last follow up. The results of 3 regimens: cyclophosphamide, enalapril, and cyclophosphamide plus enalapril were compared using chi-square test. Remission was significantly better in cyclophosphamide group (p = 0.014). Dipyridamole was prescribed in 14 patients due to thrombocytosis. Only 2 of 14 patients achieved remission although 11 patients received cyclophosphamide plus enalapril, and another 2 patients received only cyclophosphamide. Complications included hypertension (44%), cataract (40%), glaucoma (15%), short stature (17.6%), and obesity (5.9%). Recurrent infection was found in 69%, including dental caries (16.29%), urinary tract infection (14.7%), intestinal parasitic infestration (10.3%), respiratory tract infection (8.8%), and skin infection (7.4%). Chronic renal failure was found in 3 patients and portal vein thrombosis was found in 1 patient. We suggest that cyclophosphamide should be used as first line drug in difficult-to-treat nephrotic syndrome patients. Enalapril may be beneficial in some patients. Thrombocytosis may be associated with poor response to both medications. Difficult-to-treat patients also need long-term follow up and surveillance for complications due to disease and/or treatment.

Adjuvants, Immunologic↗
PubMed1991

Essential thrombocythemia: a hypercoagulable state.

Essential thrombocythemia is an entity characterized by clonal proliferation of megakaryocytes and thrombocytosis. We have analyzed the presenting manifestation of 13 patients with Essential Thrombocythemia diagnosed in the last three years. The major findings include the frequent presence of symptomatology of a hypercoagulable state with prompt improvement of these symptoms once the thrombocytosis is controlled. Constitutional symptoms, organomegaly, modest Leukocytosis and eosinophilia were also often seen. No catastrophic events were detected with a mean follow up period of 17.5 months.

Adolescent↗
PubMed1991

Regulation of murine megakaryocyte size and ploidy by non-platelet-dependent mechanisms in radiation-induced megakaryocytopenia.

Megakaryocytic macrocytosis was evaluated in mice after irradiation with 6.5 Gy 60Co gamma rays. During the second and third months after sublethal irradiation, one or more of the following abnormalities of thrombocytopoiesis was present: thrombocytopenia, megakaryocytopenia, macromegakaryocytosis, a shift to higher ploidies, and enlargement of cells within ploidy groups. After transfusion-induced thrombocytosis, reductions in megakaryocyte size were delayed or absent relative to non-irradiated mice, and there was more of a tendency to shift to lower values for megakaryocyte ploidy. Mice with radiation-induced megakaryocytopenia failed to show rebound thrombocytosis during recovery from immunothrombocytopenia, in spite of further increases in megakaryocyte size and ploidy. The findings support the hypotheses that numbers of megakaryocytes may influence the regulation of megakaryocytopoiesis even when there is an excess of platelets and that ploidy distribution is not the sole determinant of the average size of a population of megakaryocytes. After irradiation, persistent megakaryocytopenia may not severely affect platelet production under steady-state conditions, but the ability of the marrow to respond to homeostatic regulation is compromised.

Animals↗
PubMed1990

[A latent form of essential thrombocythemia presented as portal hypertension and associated with acquired von Willebrand syndrome].

A 32 year-old male patient was admitted to our hospital because of abdominal tumor. The examination on admission showed massive splenomegaly and esophageal varices although peripheral blood cell counts were within normal limits. Exploratory laparotomy was performed with the diagnosis of portal hypertension and revealed the multiple thrombus formations in the splenic vein and the extramedullary hematopoietic findings in the spleen by the microscopic examination. In vitro colony forming assay showed the formation of spontaneous erythroid colonies in cultures of progenitor cells (from peripheral blood mononuclear cells) in erythropoietin-poor medium. Increasing thrombocytosis was observed immediately after splenectomy, and hemorrhagic diathesis of nasal bleeding and gastrointestinal bleeding were also detected. The analysis of plasma von Willebrand factor (vWF) revealed the decrease of ristocetin cofactor activity and the lack of large multimeric components of vWF. These abnormal findings observed after splenectomy led to recovery through the administration of busulfan with the improvement of thrombocytosis. Accordingly, the course of the disease clearly indicated it to be the essential thrombocythemia represented as portal vein thrombosis and in latent form with normal cell counts in peripheral blood at the time of diagnosis, and subsequently, to develop into a full-blown form associated with acquired von Willebrand syndrome following splenectomy.

Adult↗
PubMed1986

[Essential thrombocythemia and hypertension as a result of stenosis of the renal artery].

Primary thrombocythemia may cause vascular thrombosis; it has been rarely involved in coronary atherosclerosis with myocardial infarction. We report three cases of renal arteries atherosclerosis occurring in association with primary thrombocythemia. These cases are three young women (20, 40 and 42 years old) with severe hypertension secondary to atherosclerosis with stenosis of renal arteries, one or both sided, and in association in one case with diffuse arterial stenosis. Systematic investigation revealed thrombocytosis with latent myeloproliferative syndrome of megacaryocytic colony. Thrombocytosis was previously present as attested by a blood count one year before (in one case) and by long-term peripheral vasomotor troubles, electively improved by aspirin (in two cases). In none of these three cases, vascular risk factors, nor hereditary vascular diseases were present. So we assume that platelets high levels are responsible for this early atherosclerosis, in keeping with the well-know role of platelets in atherosclerosis pathogenesis. Platelets investigations must be done in case of renovascular hypertension, occurring without any classical vascular risk factors.

Adult↗
PubMed1988

Splenectomy in agnogenic myeloid metaplasia and postpolycythemic myeloid metaplasia. A study of 34 cases.

A retrospective analysis of 34 successive splenectomies in 137 patients with myelofibrosis was carried out. Indications, complications, and response to splenectomy were compared between 22 patients with agnogenic myeloid metaplasia (AMM) and 12 patients with postpolycythemic myeloid metaplasia (PPMM). Painful splenomegaly, refractory hemolytic anemia, and refractory thrombocytopenia were the common indications for surgery. The best results were obtained for painful splenomegaly. For the other indications, half to three fourths of the patients improved with splenectomy. An increased incidence of excessive hemorrhage, infected hematoma, and early mortality was more common in the PPMM group and was found to be connected with large spleens, prolonged bleeding time, and prominent thrombocytopenia. Persistent thrombocytosis after surgery was more common in the AMM group. Leukemic transformation seemed to be related to thrombocytosis and to prior therapy with alkylating agents. Median survival following splenectomy was 43 months in the AMM group and 32 months in the PPMM group. We conclude that splenectomy has a role in improving the quality of life by ameliorating mechanical discomfort and decreasing transfusion requirement in the late phase of AMM. However, in patients with PPMM, because of the high complication rate, splenectomy should be carefully considered for specific indications on an individual basis.

Adult↗
PubMed1986

Thrombospondin in essential thrombocythemia.

Essential thrombocythemia is a myeloproliferative disorder characterized by frequent bleeding and thrombotic complications. On a molecular level, two abnormalities of platelet thrombospondin have been identified: abnormal glycosylation of the intact 185,000-dalton chain has been detected and a shortened form of the thrombospondin chain is present. We have used two monoclonal antibodies and Lens culinaris lectin to probe the structure of thrombospondin in the platelets from three patients with essential thrombocythemia; one patient with polycythemia vera and two patients with secondary thrombocytosis. The presence of abnormal thrombospondin fragments with molecular weights of 160,000 and 30,000 was detected in the intact platelets and in the supernatant from thrombin-treated platelets, in all of the individuals except one of the secondary thrombocytosis patients. Monoclonal antibody binding studies indicate that both fragments are produced by proteolysis at a single site, which results in the removal of a 30,000-dalton fragment from the NH2-terminal. Lens culinaris lectin-binding studies revealed that some of the carbohydrate moieties of thrombospondin are near this cleavage site. The results are consistent with the hypothesis that the abnormal thrombospondin fragments observed under conditions of increased platelet production are due to increased susceptibility to proteolysis which, in turn, may be due to defective glycosylation.

Antibodies, Monoclonal↗
PubMed1987

Platelet function tests in thalassemic children.

Platelet changes in thalassemia included prolongation of bleeding time (30%), thrombocytosis (29%), decreased platelet retention (79%), and normal PF3 release. Platelet aggregation was found to be hyperaggregation in 50%, normal in 22%, and hypoaggregation in 28% of the studied patients. Platelet changes in thalassemia can be hyper-, normal, or hypofunction. The changes are likely to be related to many factors, particularly to the progress of the disease. Platelet hypoaggregation may lead to a bleeding problem. Platelet hyperaggregation and thrombocytosis were prominent in the splenectomized patients and/or the severely anemic group; antiplatelet drugs may be indicated in these patients.

Adolescent↗