Orofacial anatomical and occlusal changes in patients with sickle cell disease in Kuwait.

Objective: Sickle cell disease (SCD) is the most common hemoglobinopathy where morphologic changes to red blood cells affect the development of hard and soft tissues. The purpose of this study is to identify the craniofacial characteristics and maxillomandibular relationship in SCD patients and compare with unaffected subjects, through cephalometric radiographic assessment. Materials and Methods: The study included 44 Kuwaiti SCD patients (20 female, 24 male) as well as 44 age and gender matched controls. Digital lateral cephalometric, radiographs were recorded. SNA and ANB angles were measured and compared. Results: The mean SNA angle was found to be higher among the SCD cases (83.00 ± 3.22) than in controls (81.78 ± 4.58), but the difference was not statistically significant, (p = 0.146). The mean ANB angle in SCD cases (5.27 ± 2.36) was significantly higher, than that in controls (3.97 ± 2.23). The difference in means was statistically significant, (p = 0.01). Almost 50% of the SCD patients had class II malocclusion and 61.5% of the patients had prognathic maxilla. Conclusions: Patients with SCD in Kuwait exhibited characteristics of skeletal class II pattern malocclusion. They also showed evidence of compensatory maxillary expansion.

Pattern of Renal Blood Flow and Renovascular Parameters in Adult Patients With Sickle Cell Disease.

OBJECTIVES: To evaluate renal blood flow patterns and renovascular parameters in adult patients with sickle cell disease (SCD) without laboratory evidence of renal impairment. METHODS: Sixty-five steady-state adult patients with SCD (50 hemoglobin SS [HbSS], 12 HbSß0 , and 3 HbSD) and 30 age- and sex-matched healthy controls were studied. The kidney length, echo pattern, peak systolic velocity (PSV), end-diastolic velocity, renal-to-aortic ratio, resistive index (RI), acceleration time (AT), and renal vein velocity were acquired, recorded, and analyzed with a 1-5-MHz curvilinear transducer through the abdomen. RESULTS: The mean age ± SD of the patients with SCD was 32.89 ± 13.89 years. The highest means for the ultrasound-measured renal length and cortical thickness in the SCD and control groups were 11.78 ± 1.30 and 11.27 ± 0.77 cm and 1.86 ± 0.41 and 1.78 ± 0.28 cm, respectively. The figures were significantly higher in the SCD group than the control group (P < .05). Fifty-nine (90.8%) patients had a mild diffuse increase in cortical echogenicity with preserved renal cortical thickness. The highest mean extrarenal PSVs in the SCD and control groups were 138.46 ± 56.32 and 101.75 ± 31.48 cm/s (P < .05). However, the highest intrarenal RI and AT in SCD and control groups were 0.69 ± 0.07 and 0.06 ± 0.02 seconds and 0.63 ± 0.05 and 0.04 ± 0.01 seconds (P < .05). There was no significant correlation between the RI, AT, and PSV among the patients with SCD (P > .05). CONCLUSIONS: Increased renal length and cortical echogenicity with elevated PSV, RI, and AT values can serve as early ultrasound changes in adult patients with SCD without renal impairment.

Right Testicular Infarction Secondary to Spontaneous Testicular Vein Thrombosis in a Child: Case Report and Literature Review.

OBJECTIVES: To describe a case of right testicular vein thrombosis in a child and to review the literature describing similar cases and their management. METHODS: An extensive literature review of the English language literature was conducted using the following databases: PubMed, ScienceDirect and Google Scholar. RESULTS: Six cases were reported previously and summarized in this article. CONCLUSION: A 14-year-old boy who suffered from spontaneous right testicular vein thrombosis was treated with right orchiectomy and oral anticoagulation. We also reviewed and summarized the previously described cases of pediatric testicular vein thrombosis.

HWA: Hypoferritinemia without anemia a hidden hematology disorder.

INTRODUCTION: Anemia is a condition, in which the number of red blood cells (RBC) and the hemoglobin (Hb) is insufficient to meet the body's physiologic needs. Hypoferritinemia without anemia (HWA) could cause masked clinical manifestations as general weakness, easy fatigability, depressed mode, and hair loss but with normal complete blood count (CBC) parameters. HWA is deferent from iron deficiency anemia (IDA) because there is no reduction in the RBC, Hb, or any of the other parameters of the CBC. In HWA, the hypoferritinemia could be missed because serum ferritin not always requested by general practitioners. MATERIALS AND METHODS: A retrospective study conducted on 6993 patients of hypoferritinemia patients from our computerized database from 2010 to 2016. The parameters investigated to detect HWA disorder were serum ferritin, RBC, Hb, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin. RESULTS: HWA is found in 130 (0.018%) hypoferritinemia patients, in a ratio 1.7-1 females to male. CONCLUSION: HWA is a masked hematology disorder which needs new nomenclature to distinguish it from IDA because they are two deferent disorders although both of them have low serum ferritin. HWA is not a latent IDA because it could happen in patients whom will not get anemia as in polycythemia patients on recurrent veinesection treatement.

Long Standing Eculizumab Treatment without Anticoagulant Therapy in High-Risk Thrombogenic Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-orphan disease affecting all hematopoietic cell types. The abnormality of red blood cells in this disease predisposes to intravascular complement-mediated hemolysis. Eculizumab is an orphan drug used to treat this rare disease. Thrombosis is the key cause of death in PNH patients in about 40% to 67% of cases. We report the case of a woman presenting with PNH complicated with serious Budd-Chiari syndrome thrombosis and with a stent inserted in the portal vein. She refused to take any anticoagulant treatment since she commenced eculizumab 4 years before. No thrombotic events happened since that time. This case could add an extra benefit for eculizumab, which could be used as an anti-thromboembolic prophylactic agent in PNH, especially in patients with thrombocytopenia, where the use of anticoagulant agents is extremely hazardous. More randomized studies might establish the use of eculizumab without anticoagulants to avoid serious bleeding that could happen in thrombocytopenic PNH patients.

Drug-Immune Thrombocytopenia with Thrombosis versus Heparin-Induced Thrombocytopenia: A Critical Clinical Controversy.

Heparin-induced thrombocytopenia (HIT) is a type of drug-induced immune thrombocytopenia (DITP). DITP is a rare and challenging clinical issue, especially when it is associated with thrombosis. A 62-year-old woman was admitted to our institution with end-stage renal failure. She received heparin for hemodialysis. Six days later, she became febrile and was treated with vancomycin and amikacin antibiotics. Two days after starting the vancomycin, she developed severe thrombocytopenia with extensive gangrenous deep vein thrombosis in her right leg, which required a below-the-knee amputation. The HIT test yielded positive results when heparin was already stopped, but her platelet count did not regenerate even after 3 months of heparin-free treatment. Courses of vancomycin treatment were given during several febrile episodes over the long period of severe thrombocytopenia. The patient was given both anti-immune thrombocytopenia and anticoagulant treatments because of both severe persistent thrombocytopenia and recurrent thrombotic episodes. The patient died as a result of severe thrombocytopenia, recurrent infection, and blood loss from the amputation site. Vancomycin is known to cause DITP, thrombosis, and immune complexes. DITP is a bleeding disorder, whereas HIT is a controversial thrombotic disorder. HIT tests can be influenced by cross-reacting antibodies and many other factors. Thus, there is no single method that can be considered 100% effective in confirming the HIT diagnosis. Anticoagulants must be used with great caution in patients with suspected DITP. Treatment of HIT-positive cases requires both clinical correlation and experience rather than reliance on HIT tests alone.

Precision of SPECT/CT Allows the Diagnosis of a Hidden Brodie's Abscess of the Talus in a Patient with Sickle Cell Disease.

Brodie's abscess is a rare subacute osteomyelitis that can be found in sickle cell disease along with other bone complications. A 21-year-old female with sickle cell disease was presenting frequently to the medical casualty department for painful vasoocclusive crises and for persistent ankle pain and swelling. Hybrid imaging with single-photon emission computed tomography-computed tomography (SPECT-CT) incidentally revealed Brodie's abscess in the talus bone of the ankle, causing persisting long-standing pain. SPECT-CT is a modern technology used to scan bone to detect both anatomical and functional abnormalities with high specificity. Brodie's abscess is a rare bone inflammation that could be a hidden cause of pain and infection in sickle cell disease. Although rare, this lesion requires more attention in patients with sickle cell disease because their immunocompromised status renders them prone to this infection.

Successful nilotinib treatment in a child with chronic myeloid leukemia.

A 16-year-old female was diagnosed incedentally with chronic myeloid leukemia (CML) in the chronic phase. She showed complete remission after 3 months of nilotinib treatment. CML is a rare malignant neoplasm in pediatric age. It is characterized by a Philadelphia chromosome, which comes from a genetic translocation between chromosomes 9 and 22. This translocation results in an abnormal fusion called BCR-ABL oncogene which encodes a chimeric BCR-ABL protein. This protein is the underlying cause of CML. Nilotinib is a newly licensed drug for CML in adults. Structurally, it is similar to imatinib (the older tyrosine kinase inhibitor), but it is much more potent in inhibiting BCR-ABL due to its much increased affinity for its binding site. Specific guidelines for CML treatment in children have yet to be determined. In our patient, nilotinib was used as an off-label drug because it is not licensed for children. According to the pharmacokinetic response to drugs, children cannot be considered small adults irrespective of their weight. Off-label drug use based on evidence that it is the best treatment available is an important tool in the hands of expert treating physicians.

Successful management of severe refractory acquired immune bleeding disorder: Prior to insisting surgery.

INTRODUCTION: Acquired bleeding disorders are rare and may be missed before surgery. Additionally, they may be refractory to conventional treatments. PRESENTATION OF CASE: A 50-year-old patient experienced prolonged post-operative bleeding when his bleeding disorder was missed prior to his undergoing inguinal herniorrhaphy. Post-operative investigations revealed severe acquired von Willebrand syndrome associated with a monoclonal gammopathy of undetermined significance. A few months later, he required umbilical herniorrhaphy, but he did not respond to attempts to raise his von Willebrand factor antigen and activity levels using conventional therapies, including desmopressin, cryoprecipitate, intravenous immunoglobulin, and Von Willebrand factor concentrate. A triple therapy combination of dexamethasone, intravenous immunoglobulin, and mycophenolate mofetil was administered, with a successful and sustained response, lasting about 2 months. The surgery was performed safely, without any complications. DISCUSSION: Conventional acquired von Willebrand syndrome treatment is usually aimed at replacing von Willebrand factor or stimulating its secretion from storage in endothelial cells. In the present case, the alternative treatment was directed against both the humoral and cell-mediated immune mechanisms. CONCLUSION: This case of acquired bleeding disorder showed that more attention must be given to a patient's coagulation profile, even if only very minor laboratory coagulation derangements are detected prior to surgery, to avoid missing such rare disorders. The described triple therapy demonstrated good effects and may be considered for inclusion in a controlled randomized study to determine its usefulness for other surgeries delayed due to severe acquired bleeding disorders. To the best of our knowledge, this triple combination treatment has not been previously used for the treatment of severe acquired bleeding disorders that are refractory to conventional therapies.

Severe thrombocytopenia in a patient with hepatitis C treated with eltrombopag from off-label drug use to on-label drug use: a case report.

INTRODUCTION: Off-label drug use refers to drug use beyond the specifications authorized for marketing. Eltrombopag is a new thrombopoietin receptor agonist which was used successfully in this critical case of thrombocytopenia associated with hepatitis C infection before it became an approved drug for such cases. CASE PRESENTATION: A 56-year-old Kuwaiti woman with hepatitis C virus infection was treated with pegylated interferon α-2a and ribavirin, laboratory test results prior to therapy were within normal values. After 4 weeks of that treatment, she developed neutropenia and severe thrombocytopenia. Her hepatitis C virus treatment was stopped for many years until eltrombopag was used as an off-label drug with an episode of severe thrombocytopenia. Her platelets count returned to normal level when triple therapy for hepatitis C virus was used successfully. CONCLUSIONS: An off-label drug should be used only when it is the best available drug, based on evidence from on-going multicenter trials. It could be life saving for some patients in critical situations. However, clinical use of eltrombopag later confirmed that it is a safe and effective drug for immune thrombocytopenic purpura or thrombocytopenia associated with hepatitis C virus infection.

Splenectomy complicated by sustained extreme thrombocytosis and extensive portosplenomesenteric vein thrombosis in pyrimidine 5'-nucleotidase deficiency.

Reactive and redistributional thrombocytosis is a well-known postsplenectomy occurrence .Usually it is transient and it rarely reaches extreme levels. We report a rare case of haemolytic anaemia where splenectomy was carried out following trauma to a massively enlarged spleen and was followed by extreme sustained thrombocytosis associated with extensive portal, splenic and mesenteric vein thrombosis despite standard antithrombotic prophylaxis.

Can lenalidomide play a role in the management of scleritis?

Lenalidomide is an immunomodulatory agent that was approved for the treatment of a monoclonal bone marrow disorders, myelodysplastic syndrome del(5q)(MDS del(5q)), in 2005; the drug was subsequently also approved for the treatment of refractory multiple myeloma, a bone marrow malignancy of the B-lymphocyte lineage. The purpose of this study is to report a case of MDS del(5q) in a female patient, which was most likely secondary to the immunosuppressive drugs that the patient was taking for scleritis. After lenalidomide treatment, the patient's haematological symptoms rapidly resolved and she became transfusion independent, with normal haemoglobin levels. This medication also helped control her dependence on high doses of oral prednisolone. The patient continued to receive treatment with low-dose lenalidomide, and her scleritis has been in long-term remission for 3 years. A larger prospective study can further define the role of lenalidomide in the management of scleritis.

Complete Remission of del(5q) Myelodysplastic Syndrome after 7 Days of Lenalidomide Therapy Gives an Alert!

Myelodysplastic syndrome (MDS) refers to a group of haematological, monoclonal disorders. A 50-year-old woman was diagnosed with MDS 5q deletion syndrome [del(5q)], becoming dependent on blood transfusion after long-term treatment with cytotoxic drugs for chronic scleritis. Lenalidomide therapy (10 mg/day) led to profound pancytopaenia, followed by recovery of her blood cell counts. A cytogenetic study, repeated 4 months after lenalidomide treatment, revealed complete remission after only 1 week of lenalidomide therapy. Lenalidomide was approved for low- and intermediate-1-risk MDS, where it normalises platelet counts and induces haematological and cytogenetic remission. This patient has remained transfusion independent for 3 years by continuing on a minimal maintenance dose of lenalidomide. Starting MDS patients on lenalidomide has to be done cautiously or with only 5 mg/day because of the potentially high sensitivity of the stem cells to this immunomodulatory agent in MDS patients.

Use of romiplostim in a hemodialysis patient with primary immune thrombocytopenia.

OBJECTIVE: To present the case of a patient with primary immune thrombocytopenia (ITP), renal impairment, and chronic hepatitis C virus (HCV) infection who was treated with platelet transfusions, intravenous immunoglobulin (IVIG), corticosteroids, eltrombopag, rituximab, and romiplostim in an attempt to raise platelet counts to a clinically acceptable level. CASE SUMMARY: A 71-year-old man with end-stage renal disease (ESRD) was on maintenance hemodialysis and had long-term diabetes mellitus, chronic obstructive pulmonary disease, and other comorbidities. He was admitted with epistaxis, severe thrombocytopenia, and a platelet count of 4 × 10(9)/L. Platelet transfusions, treatment with IVIG, corticosteroids, eltrombopag, and rituximab resulted in transient and inadequate increases in platelet counts. Further bleeding manifestations, including epistaxis, melena, hematomas, and ecchymotic patches prompted treatment with blood product concentrates and a higher dose of eltrombopag, resulting in a further lack of clinical response. After 6 weeks of failed treatment attempts, initiation of weekly treatment with romiplostim 5 µg/kg resulted in rapid stabilization (within a week) of platelet counts in the range of 200 × 10(9)/L. The patient was discharged, with subsequent dose adjustment of weekly romiplostim treatment to 2.5 µg/kg, continued hemodialysis, and a return to normal daily activities. DISCUSSION: The primary clinical concern in this elderly patient with multiple comorbidities was to lower the bleeding risk associated with consistent thrombocytopenia. Despite the lack of clinical data to support the efficacy and safety of romiplostim in patients with ITP and renal impairment, stimulation of platelet production with romiplostim was a reasonable approach in view of the bleeding risk and following nonresponse to treatment with corticosteroids, IVIG, eltrombopag, and rituximab. To our knowledge, this case represents the first successful use of romiplostim to manage primary ITP in the presence of ESRD and concurrent chronic HCV infection in a patient on hemodialysis. CONCLUSIONS: Romiplostim appears to be a viable option for treatment of ITP in a patient with ESRD and chronic HCV infection following nonresponse to treatment with corticosteroids, IVIG, eltrombopag, and rituximab.

Lymphocyte subsets in healthy adult Kuwaiti Arabs with relative benign ethnic neutropenia.

Relative and absolute neutropenia is frequently seen in the healthy adult Kuwaiti Arab population. Fluorescent monoclonal antibody labelling followed by flow cytometry was used to determine the lymphocyte subsets in 48 normal healthy individuals in the Kuwaiti adult population (24 males and 24 females, age 17-59 years) with relative or absolute neutropenia, and this was compared to age-matched controls (64 males and 63 females). The mean haemoglobin levels were 13.6+/-1.5 and 13.7+/-1.5 g/dl in the neutropenic and control groups, respectively. White blood cell counts, absolute neutrophil and lymphocyte counts in neutropenic individuals with the corresponding reference range, taken from the control subjects (in parenthesis) were: WBC, 6.7+/-1.6 x 10(9)/l (4-10.4 x 10(9)/l), neutrophils, 2.7+/-0.8 x 10(9)/l (1.87-6.63 x 10(9)/l), lymphocytes, 3.3+/-0.9 x 10(9)/l (1.4-3.62 x 10(9)/l). Absolute values of lymphocytes, CD2+, CD3+, CD19+, CD4+, CD8+, HLADR+ and CD45RA+ cells were significantly higher in the neutropenic group. The range of values with the corresponding reference ranges, in parenthesis, were: CD2+, 1.61-4.30 x 10(9)/l (0.95-2.99 x 10(9)/l), CD3+, 1.37-4.16 x 10(9)/l (0.83-2.71 x 10(9)/l), CD19+, 0.16-1.09 x 10(9)/l (0.05-0.61 x 10(9)/l), CD4+, 0.70-2.89 x 10(9)/l (0.45-1.65 x 10(9)/l), CD8+, 0.57-1.80 x 10(9)/l (0.29-1.17 x 10(9)/l), HLADR+ 0.27-1.74 x 10(9)/l (0.02-0.62 x 10(9)/l), CD45RA, 0.90-4.63 x 10(9)/l (0.34-2.05 x 10(9)/l), respectively. The levels of natural killer cells, CD56+ cells were significantly lower compared to controls while the values of memory T lymphocytes, CD45RO+ were comparable to controls. These results indicate that difference in the leukocyte subpopulations may also be indicative of differences in the lymphocyte subpopulations and that reference ranges for these cell types in healthy neutropenic and non-neutropenic individuals should be established.