How I treat immune thrombocytopenia – a global view

As haematologists, we always seek to follow standardized guidelines for practice and apply the best treatment within our means patients with blood diseases. However, can never an exact formula. Opinions differ as approach; sometimes more than one approach results in identical outcomes, or treatments only by manner which they fail. Furthermore, haematologist is faced constraints relating local economic environment. Patients, too, are not same world over. Early presentation common developed world, patient’s understanding of disease process. This turn has impact on way managed, rigorousness patient adhesion schedule outcome. For these reasons, given starting conditions, will be treated differently according institute country in. In this series global views, have tasked experts from around describe their management plan rationale a specific presentation. Here explore autoimmune thrombocytopenia (ITP) institutions six different nations. We conclude expert field comparing contrasting styles considering merits limitations. The case history questions posed shown Box 1 responses summarized Table 1. Oral prednisolone Occasionally afford IvIg Treatment based platelet counts. if counts < 30 × 109/l Second line consist dapsone, azathioprine splenectomy. If failure: Danazol option those otherwise Rituximab TPO-RAs Repeated IvIg, splenectomy, rituximab*, romiplostim* breastfeeding: Remove accessory spleens, No limitations Prednisolone Start mg/kg/day few days reduce 20–25 mg/day even less response I would advise risk ITP recurrence worsening during second pregnancy possible complications mother fetus. women active wanting pregnancy, consider ‘preparing’ woman safe using long-term benefits treat symptomatic and/or count 20 109/l. course no IvIg: Romiplostim romiplostim bleeding: rituximab splenectomy Observation Check baby. bleeding. breastfeeding. Splenectomy previous expectations Platelet concentrate Eltrombopag, romiplostim, hope that exercise brings home practicing clinicians there ‘right’ manage patients. There things learn other experts’ practice. Moreover, much colleagues working lower-resourced economies. teaches us should nuanced perception how why worldwide. A 26-year sees her general practitioner because petechiae lower extremities. She unremarkable prior episodes bleeding normal menstruation pattern. laboratory workup reveals nothing out ordinary except 5 but positive test (hitherto unknown patient). referred haematology department. inform result! points toward being newly diagnosed at early stage although it important alert alternative diagnoses, may related. spurious unlikely petechiae, film examined urgently repeated, along routine baseline investigations.1 Thrombotic thrombocytopenic purpura (TTP) seems finding clinical-laboratory work-up, both acquired hereditary TTP present commonly rapidly excluded review haemolytic screen. It unusual, unreported, isolated thrombocytopenia. gestation accurately assessed dating ultrasound scan pregnancy-related disorders, haemolysis, elevated liver enzymes low platelets, (HELLP), pre-eclampsia acute fatty seen first trimester extremely rare trimester. Hereditary severe also adult life. While initially screen absence any pre-existing personal family history, keep mind subsequently proves unsatisfactory. Assuming trimester, what appear score, my initial oral prednisolone. Doses routinely used non-pregnant ITP, state, aim taper steroids cessation 6 weeks. ongoing likely needed, manifestation start dose convenience, 25 mg daily (one tablet) adjust either up down, depending response. Although high level evidence support strategy, opinion2 experience guide decision. After satisfactory effect therapy you instituted uneventful birth healthy boy, she without symptoms 3 years, when seeks your advice planning become pregnant. wish counsel possible, ‘high-risk pregnancy’ monitoring required confirmation (assuming was confirmed stage). Published reports3 indicate exacerbation acceptable outcomes nearly favourable. succeeds becoming pregnant, once displays pronounced drop counts, time 58 109/l, signs therapeutic again, discover its effectiveness increasing 70–90 started impending delivery. monitor closely. dropped below threshold (<20 petechiae/bruising), reinstate successfully (prednisolone doses previously indicated). Nearer delivery, goals change such > 50 delivery (irrespective method) epidural anaesthesia desired, 80 To achieve above, were enough time, increase count. successful, urgency count, use intravenous immunoglobulin (IvIg). 1g/kg 2 very urgent 0·4 g/kg (there higher dose, so preference schedule). Therapeutic strategies beyond corticosteroids rarely needed pregnancy. Anti-D available Australia. further measures pregnancy4 useful steroid sparing, prolonged periods. trimester,5 resorted this. Thrombopoietin receptor agonists (TPO-RAs) short term probably safe,6 data limited so, currently, last resort. birth, follow-up post-partum, platelets now two consecutive occasions 20–30 Generally, remits some degree post-partum. might still occur, unless bleeding, factors situation treat. declined developed, next step depend breastfeeding status mother’s willingness switch formula feeding. willing cease, then choices limited. assessment determine whether swiftly (corticosteroids, IvIg) slower recovery reasonable goal. latter case, 100 weekly 4 choice. Younger females, particularly broader diathesis, group who respond (Bird, manuscript preparation). funded nationally Australia generic drug, funding self-funding generally feasible. Full hepatitis B serology checked before rituximab. Breastfeeding barrier rituximab.7 Government restrictions require medical contraindication (patient considered). Unfortunately, essentially precludes cost 60% average annual gross income. Numerous ‘traditional’ little base available, preference, all inclusion/exclusion criteria met, invite participate clinical trial. Other mentioned trials cannot accessed include (most commonly) mycophenolate mofetil (dexamethasone, high-dose methylprednisolone) and, uncommonly, danazol, vincristine ciclosporin. Arrangements exist hospital individual drugs Australian Pharmaceutical Benefits Scheme. context, found H. pylori screening eradication East Asian (particularly Japanese) ethnicity. most cause ITP.8 According primary ITP. initiation Thailand depends develops related (usually 109/l), started. gestational 36 weeks, weeks more, prepare caesarean required. corticosteroids, dexamethasone. life-threatening dexamethasone transfusion. addition, cases intracerebral haemorrhage, emergency considered centres. Thailand, reimbursed patient, recommend transplacental transfer dexamethasone.9 Dexamethasone approaching promote fetal lung maturity. Because tuberculosis prevalent suggest chest X-ray (with shield) after counselling about risks benefits. testing stool parasites intermittent fasting sugar while taking recommended. First, husband vice versa, including therapy. fall, stable Judging tends decrease hopefully, well child, pregnancy; also, mortality rate low.10 effects been reported increased stillbirth, loss, preterm post-partum haemorrhage.10, 11 add maternal risks, infection, hyperglycaemia, hypertension, osteopenia cleft palate fetus.9, 12 accept decides conception request X-ray, done consult dentist dental care, check full (FBC) investigations. conception, FBC every 1–2 months frequently abnormal. target 30–50 Hence, achieved already. continue above. did prednisolone, discuss options Selection stage, severity adverse effects, co-morbidity cost. dexamethasone, reserved significant observation offered 10 concerning. duration year, making diagnosis chronic ITP.13 Thus, decreased above currently used. moderate-dose maintain options, not, potential stops breastfeeding, azathioprine, cyclophosphamide danazol. high-cost (low-dose standard-dose) eltrombopag offered. wants (breastfeeding least h ingestion azathioprine14). Finally, does unacceptable elective appropriate preoperative vaccination. confirm bone marrow examination send off relevant tests, viral borne viruses, prothrombin activated partial thromboplastin systemic lupus erythematosus. like rule possibilities, non-severe aplastic anaemia, hypocellular myelodysplastic syndrome tuberculous granulomas involving marrow. counselled continued, need remain close follow-up. detailed conversation had regarding come regular ante-natal period. Since clinically stable, showed good tapering slowly down lowest towards end third stop 2–4 delivery.15 warn 30% possibility relapse requiring Therefore, became needs under monitoring. dapsone.16 received presently During able reconsider hypertension diabetes. initiate (2–3 mg/kg/day) dapsone (1–2 haemoglobin watching development skin rash. Based upon drugs, expect rise 50% general, take between 8 improvement apparent. low-dose ciclosporin divided doses, pressure renal function. occasionally find unresponsive maintains 10–20 patients, section planned obstetric indication, performing time.16 post–partum, warrants treatment, since current 109/L. mg/kg/day). Corticosteroids 0·5 added mucocutaneous Either period 3–6 failed; failure considered. non-responder dependent features could kept till manifestations therapy, discussion surgical versus non-surgical options. My published centre show remission rates 70% 5- 10-year overall survival 90%. one-time procedure cheaper procedure, resources. resource constraints, danazol pulse cyclophosphamide. four – romiplostim. Generic India considered.17 regard disorder due lack information members disorders. suggestion conditions underlying findings (acute sepsis disseminated intravascular coagulation pre-eclampsia/HELLP syndrome, suggestive collagenosis, peripheral changes microangiopathy malignant haematological disease). apart thrombocytopenia, diagnose having tested human immunodeficiency virus (HIV) C infection. Pregnancy unnoticed unusual assume early, unrelated. Gestational occurs usually later rarely, ever, serious, corticosteroids. Two regimens suggested: mg/kg/day, tapered 40 mg, fixed days, one–three courses. increasingly popular here ‘common’ though firm superiority over response.18 dosage, (0·25 mg/kg/day), investigated ITP,19 recently. confers exposure fetus, suggested factor palate. large Danish cohort study, 832 636 live births, infants prescribed corticosteroids.20 Nevertheless, precaution, soon thus minimizing additional benefit obvious disadvantages pregnant patient. allows single episode mild problem must unravelled planning, cases, encourage proceed plans. relapse/progression pregnancy,3 reluctant give accurate number. indication pre-emptive intervals, example month, indicated order avoid undetected crucial point situation. (58 109/l) safe,1, 21 tendency. arrange frequent informed requires Most obstetrical manoeuvers, section, perhaps excluding vacuum extraction scalp electrodes, performed 109/l.21 Let regimen before. maximum 90 significantly reduced mg/day. Under circumstances, peripartum expected high, scheduled none novel, interventions attractive, experience, intervention repeated quite expensive, challenge expansion plasma volume burdened anaemia complicating aseptic meningitis. chance lasting years 70%, allowing pregnancies. Laparoscopic minimal individuals. optimum timing Medical alternatives TPO-RA rituximab, success. reported, estimates, thus, unreliable. Both cross placental fetus would, therefore, exposed ‘physiological’ side megakaryocyte hyperplasia B-cell depletion. response, often several taken into consideration context. immunosuppressants, mofetil, regarded success uncertain late. British retrospective study month 107 pregnancies uniformly successful outcome, manageable haemorrhage (defined 500 ml loss) problem.10 Eighty per cent both. One anti-D immunoglobulin; Denmark. minimal. situation, stay calm. deterioration know that. restricted, You speculate inactivated absorbed child’s gastrointestinal channel. spleen removed reasons removed, investigating spleens eliminated. steroid-saving immunosuppression, preferably Provan et al. recently updated international consensus report corticosteroids1 classified ‘robust’ (TPO-RAs fostamatinib) ‘less robust’ (other vinca alkaloids). Denmark minimal, admittedly, long record usefulness far expens