Extreme Reactive Thrombocytosis Caused by Obstructive Nephrolithiasis and Pyelonephritis.

Platelet counts in reactive thrombocytosis rarely exceed 1000 × 109/L. We present the case of a male patient, aged 80 years, with quiescent rheumatoid arthritis who was found to have a platelet count of 1011 × 109/L on routine laboratory testing. The patient was initially asymptomatic but developed leukocytosis to 23.1 × 109/L on hospital day 2. Diagnostic work-up revealed obstructive nephrolithiasis and pyelonephritis, and the thrombocytosis and leukocytosis gradually resolved with empiric antibiotic treatment and ureteral stent placement. Tests for myeloproliferative disorders, including JAK-2V617F mutation, BCR-ABL for chronic myeloid leukemia and acute lymphocytic leukemia, and myeloproliferative neoplasms (MPL/CALR), were negative. Physicians should be aware that in rare cases reactive thrombocytosis can exceed 1000 × 109/L, and that markedly elevated platelet counts in the setting of urinary tract infections may be an early sign of obstructive uropathy.

Anemia in Celiac Disease: Multiple Aspects of the Same Coin.

Extraintestinal manifestations of celiac disease (CD) are an integral part of the disease's clinical profile and, frequently, appear as the presenting feature. Given that anemia in CD may be multifactorial, increased awareness is needed on the part of treating physicians, and especially hematologists, to screen for CD. In this study, we highlight anemia as the presenting feature of CD which has remained undiagnosed for several years. In patients with a positive antibody testing or high suspicion of CD, endoscopy with a biopsy of the small intestine is performed, as it is considered the "gold standard" for diagnosing CD. Since most of the manifestations of CD are preventable or treatable with a gluten-free diet, an early diagnosis is vital for the prevention of serious and potentially lethal complications.

Postpartum vertebral artery dissection: case report and review of the literature.

BACKGROUND: Hypertensive disorders of pregnancy are associated with vascular complications, including ischemic stroke and cervical artery dissection. Vertebral artery dissection (VAD), however, is rare. We describe a 31-year-old female who presented with vertigo, nausea, and vomiting and was found to have a VAD. In addition, we discuss the presentation, differential diagnosis, and pathogenesis of this uncommon but clinically significant vascular event and summarize other cases of vertebral artery dissection described in the medical literature. CASE PRESENTATION: A 31-year-old Hispanic woman presented 10 days postpartum with a one-day history of vertigo, nausea, vomiting, and frontal headache. The patient's pregnancy course had been complicated by preeclampsia, chorioamnionitis, and iron-deficiency anemia, and her delivery was complicated by acute hemorrhage. Physical examination was significant for left leg ataxia. Laboratory studies showed marked thrombocytosis. Emergent computed tomography (CT) scan of the head was obtained and revealed a left cerebellar ischemic large vessel stroke. Subsequent CT angiography of the head and neck showed a left VAD. Based on correlation of the clinical history and laboratory and imaging findings, a diagnosis of vertebral artery dissection secondary to reactive (secondary) thrombocytosis from overlapping iron-deficiency anemia and acute hemorrhage was established. The patient was started on a heparin infusion and experienced significant improvement after a four-day hospitalization. CONCLUSION: VAD is a rare but important cause of neurologic symptoms in the postpartum period and should be considered in the differential diagnosis for women who present with headache and/or vertigo. Women aged 30 years or older and those with a history of a hypertensive disorder of pregnancy are at particularly high risk. Prompt diagnosis and management of VAD is essential to ensure favorable outcomes.

Quantification of IGF-1 receptor is useful in the differential diagnosis of essential thrombocytosis from reactive thrombocytosis.

BACKGROUND: To make a definite diagnosis of essential thrombocytosis (ET) from reactive thrombocytosis (RT), the most reliable criteria are the presence of driver mutations, namely JAK2, CALR, or MPL gene mutations. In the absence of these driver mutations, so-called triple-negative ET, the differential diagnosis could be difficult. Although bone marrow biopsy could be helpful, it may be difficult in some cases, to do gene sequence analysis to identify other clonal marker gene mutations than the driver mutations, as only very few were found. METHODS: IGF-1R quantification by flow cytometry in mononuclear cells (MNC) from peripheral blood was performed in 33 patients with ET (untreated or off treatment with hydroxyurea), 28 patients with RT, and 16 normal volunteer controls. RESULTS: We found IGF-1R levels were significantly elevated in ET patients compared to RT patients or controls. A cutoff value of 253 was chosen from the logistic regression to predict each patient's group, a value ≥253 meant that a patient belonged to the ET group (sensitivity 96.4% and specificity 68.6%). CONCLUSION: We suggest that adding quantification of IGF-1R in blood MNC by flow cytometry is useful in differentiating ET from RT.

A Review and Assessment of Drug-Induced Thrombocytosis.

OBJECTIVES: The purpose of this article is to review the current literature on drug-induced thrombocytosis with the goal of critically assessing causality and providing a comprehensive review of the topic. Thrombopoietic growth factors, such as thrombopoietin-receptor agonists (romiplostim and eltrombopag) and erythropoietin are not included in our review. DATA SOURCES: The literature search included published articles limited to the English language and humans in MEDLINE, EMBASE, and Web of Science databases. MEDLINE/PubMed (1966 to September 2018) was searched using the MeSH terms thrombocytosis/chemically-induced and thrombocytosis/etiology. EMBASE (1980 to September 2018) was searched using the EMTAGS thrombocytosis/side effect. Web of Science (1970 to September 2018) was searched using the search term thrombocytosis. References of all relevant articles were reviewed for additional citations and information. STUDY SELECTION AND DATA EXTRACTION: Review articles, clinical trials, background data, case series, and case reports of drug-induced thrombocytosis were collected, and case reports were assessed for causality using a modified Naranjo nomogram. DATA SYNTHESIS: Drug-induced thrombocytosis, a form of reactive thrombocytosis cannot be easily differentiated from more common etiologies of reactive thrombocytosis. In all, 43 case reports of drug-induced thrombocytosis from a wide variety of drugs and drug classes were reviewed using a modified Naranjo probability scale that included criteria specific for thrombocytosis. CONCLUSIONS: Drug-induced thrombocytosis is a relatively rare adverse drug reaction. The strongest evidence of causality supports low-molecular-weight heparins and neonatal drug withdrawal. Weaker evidence exists for all-trans retinoic acid, antibiotics, clozapine, epinephrine, gemcitabine, and vinca alkaloids.

Assessment of procoagulant potential in patients with reactive thrombocytosis and its association with platelet count.

OBJECTIVE: We aimed to determine hemostatic changes and characterize the procoagulant potential among patients with reactive thrombocytosis (RT). METHODS: Sixty patients with RT (median platelet count 718 × 109 /L) and 20 healthy persons were tested for complete blood count, C-reactive protein, von Willebrand factor (VWF), factor VIII and fibrinogen, and thrombin generation. Platelet studies, including light transmission aggregometry and Cone and Plate(let) Analyzer, were also conducted. Reticulated platelets and platelet P-selectin expression were measured using flow cytometry. RESULTS: Compared to patients with mild thrombocytosis (platelet count 500-700 × 109 /L; n = 27), those with moderate-to-severe thrombocytosis (platelet count >700 × 109 /L; n = 33) had significantly higher fibrinogen, factor VIII, and VWF antigen and activity levels; higher endogenous thrombin potential, peak thrombin generation and velocity index levels, and shorter time-to-peak thrombin level. VWF antigen and activity, fibrinogen, and factor VIII were positively associated with platelet count, whereas VWF activity/antigen ratio was inversely correlated. In a multivariate analysis of RT and control participants, only platelet count predicted endogenous thrombin potential with a positive-linear correlation. No patients developed acquired von Willebrand syndrome. CONCLUSIONS: As determined by thrombin generation, RT was associated with in vitro prothrombotic tendency, which correlated with platelet count. This may explain the increased thromboembolic risk previously reported in patients with RT.

Fatal pulmonary embolism following splenectomy in a patient with Evan's syndrome: case report and review of the literature.

BACKGROUND: Evans syndrome (ES) is a rare disease characterized by simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) with or without immune neutropenia. Splenectomy is one of the treatment options for disease refractory to medical therapy. Venous thromboembolism (VTE) following splenectomy for hematological diseases has an incidence of 10%. CASE PRESENTATION: Here we describe a case report of a young patient hospitalized with severe hemolytic anemia with Hgb 4.8 g/dl. He developed thrombocytopenia with platelet nadir of 52,000/mm3, thus formally diagnosed with ES. He failed standard medical therapy. He underwent splenectomy and had a fatal outcome. Autopsy confirmed the cause of death as pulmonary embolism (PE). CONCLUSIONS: This case report and review of the literature highlight important aspects of the association between VTE, splenectomy, and hemolytic syndromes including the presence of thrombocytopenia. The burden of the disease is reviewed as well as various pathophysiologic mechanisms contributing to thromboembolic events in these patients and current perioperative prophylactic anticoagulation strategies. Despite an advancing body of literature increasing awareness of VTE following splenectomy, morbidity and mortality remains high. Identifying high risk individuals for thromboembolic complications from splenectomy remains a challenge. There are no consensus guidelines for proper perioperative and post-operative anti-coagulation. We encourage future research to determine which factors might be playing a role in increasing the risk for VTE in real time with hope of forming a consensus to guide management.

Severe anemia from heavy menstrual bleeding requires heightened attention.

OBJECTIVE: The objective of the study was to analyze the behaviors of women that resulted in menstrually related severe anemia (hemoglobin <5 g/dL) from a single public hospital serving indigent women. STUDY DESIGN: This was a retrospective cohort study of all women identified as having been treated at Harbor-UCLA Medical Center for excessive menstruation (International Classification of Diseases, ninth revision, codes 285.9, 6256.2) and hemoglobin values less than 5 g/dL in the 6 years from 2008 to 2013. RESULTS: Approvals were obtained from the Human Subjects and Research Committees. This search identified 271 women with those 2 diagnoses; 122 were excluded because their severe anemia had nonmenstrual causes. The remaining 149 women had 168 episodes with hemoglobin levels below 5 g/dL attributed to chronic excessive menstrual bleeding. Mean age was 41 years (range, 19-55 years). Mean body mass index was 28.9 kg/m(2) (range, 18-57 kg/m(2)); 58.2% were actively bleeding at presentation, and 90.4% reported chronic excessive blood loss. Two thirds recognized heavy bleeding that had persisted for more than 6 months without seeking help. However, 7.8% described their bleeding as normal, and 40.5% had received at least 1 previous transfusion. Mean nadir hemoglobin was 4.15 g/dL (range, 1.6-4.9 g/dL). Mean corpuscular volume was 62.2 fL (range, 47.7-99.8 fL) and mean corpuscular hemoglobin concentration was 29.2 g/dL (range, 25.7-33.6 g/dL). Nearly a quarter had reactive thrombocytosis, which might have created a hypercoagulable state. Bleeding was ultimately attributed to leiomyoma in 47.9%; cancer was detected in 4.8%. A total of 33.9% were discharged without being offered any therapy to prevent subsequent bleeding; 3.0% declined any medical therapy; 35.1% were lost to follow-up prior to receiving effective therapy; and 26.8% had multiple subsequent transfusions before seeking/receiving definitive treatments. CONCLUSION: Even when faced with potentially life-threatening anemia because of chronic, excessive menstrual blood loss, some women are not impressed with the serious nature of their problem. Women will benefit from recognizing the health consequences of chronic excessive blood loss. Chronic excessive blood loss should be treated as both an urgent and potentially recurrent problem; physicians should address this clinical concern proactively.

Incidental thrombocytosis: Should it concern the anesthesiologist?

Preoperative thrombocytosis, often detected incidentally in surgical patients and inadvertently overlooked, has important implications for the anesthesiologists. The primary form is a chronic clonal myeloproliferative disorder usually affecting adults while the secondary type is a benign reactive disease commonly found in children. Serious perioperative hemostatic complications are reported in primary thrombocytosis and hence, a detailed preoperative evaluation and initiation of therapy to lower the platelet count (PC) is required before undertaking surgery. Patients with reactive thrombocytosis however, usually have complication-free surgeries, and if there is no prior evidence of hemostatic complications and the reactive cause can be identified, no specific perioperative intervention may be required. A thorough preanesthetic checkup and implementation of basic thrombo-prophylaxis measures in all patients with a raised PC is advocated. We present here our experience with three infants diagnosed with high preoperative PC, presumably due to reactive causes, who underwent uneventful neurosurgeries at our institution.

Does reactive thrombocytosis observed in iron deficiency anemia affect plasma viscosity?

OBJECTIVE: The accompanying thrombocytosis is referred to as the major factor associated with thromboembolism in iron deficiency anemia (IDA). Increased viscosity may increase the risk of thrombosis. We hypothesized that increased platelet count -with reactive thrombocytosis- might also affect plasma viscosity. We planned to evaluate the influence of normal and high platelet count on plasma viscosity in IDA patients. MATERIAL AND METHODS: The patient population consisted of fifty-three newly diagnosed and untreated women aged between 18 and 62 years with IDA. Group 1 consisted of 33 patients, platelet levels below 400 x 10(9)/L. Group 2 consisted of 20 patients, platelet levels above 400 x 10(9)/L. Measurements of plasma viscosity were performed using Brookfield viscometer. RESULTS: Mean plasma viscosity was found as 1.05 ± 0.08 mPa.s. in Group 1, and 1.03 ± 0.06 mPa.s. in Group 2. Mean plasma viscosity was not statistically different. White blood cell count was significantly higher in Group 2. Vitamin B12 levels were significantly higher in Group 2, while folic acid levels were higher in Group 1 (p=0.011 and p=0.033). Plasma viscosity was correlated with erythrocyte sedimentation rate (r=0.512 p=0.002) in Group 1 and inversely correlated with vitamin B12 (r=-0.480 p=0.032) in Group 2. CONCLUSION: Despite the significant difference between groups in terms of platelet count, no significant difference was detected in plasma viscosity and this finding could be explained as the following; 1-These platelets were not thrombocythemic platelets; 2-Similar to the theory about leukocytes, higher platelet counts - even non-thrombocythemic - may increase plasma viscosity; 3-Evaluating platelet count alone is not sufficient and the associating red-cell deformability should also be taken into account; and 4-Although other diseases that could affect viscosity are excluded, some definitely proven literature criteria such as fibrinogen, hyperlipidemia, and the inflammatory process should also be evaluated by laboratory and clinical measures.