Sickle cell anaemia. GP Education Update 19 th July 2018 Croydon University Hospital. Arne de Kreuk Consultant Haematologist

Transcription

1 Sickle cell anaemia GP Education Update 19 th July 201 Croydon University Hospital Arne de Kreuk Consultant Haematologist

2 Outline: Prevention of sickle cell related complications; annual review Identification of those at (high) risk Role of the GP Pain management Iron and folic acid

3 Sickle Cell Disease: a Few Facts About 90% of people survive to age 20. Close to 50% survive beyond the fifth decade. Estimated mean survival for people with sickle-cell was 53 years old for men and 5 years old for women with homozygous SCD. In the UK it is thought that between 12,000 and 15,000 people have sickle cell disease with an estimate of 250,000 carriers of the condition in England alone.

4 Sickle Cell Disease at CUH Currently 31 registered patients on National Haemoglobinopathy Register Around 520 people with SCD attending the services 1 new-borns with significant HB pathy last year

5 Sickle Cell Disease at CUH ADULTS Non- Elective Admissions Total Cost of NEL Admissions Average Cost per Admission Total Length of stay Average Length of Stay Total Excess Bed Days 15/ ,97 1, / ,969 1, / ,045 1, PAEDS Non- Elective Admissions Total Cost of NEL Admissions Average Cost per Admission Total Length of stay Average Length of Stay Total Excess Bed Days 15/ ,671 1, / ,243 2, / ,734 1,

6 Sickle Cell Disease: Cost x Facts Average cost per admission: 2,000 Croydon: 0.7 non-elective admissions per patient per year. UK-wide: 12,000 15,000 patients with SCD Hospital episode Statistics (2012/3): 13,300 finished consultant episodes Prevention of 1 non-elective admission per patient would save CCGs over 7 million nationwide

7 Organisation of Care for SCD: Improving Haemoglobinopathy Pathways through Operational Delivery Networks: South Thames Sickle Cell & Thalassaemia Network (STSTN) Hub and Spoke model Guarantee same level of care Shared protocols and guidelines MDT Service level agreements Clinical Governance Arrangements Community / primary care role not defined! GP representative highly desired

8 What is sickle cell disease?

9 What is sickle cell disease?

10 Triggers for polymerisation: Hypoxia Infections Dehydration Acidosis Sudden changes in temperature Stress Pregnancy

11 Infarction and Organ Damage Vaso-occlusion Hypoxia Bone Marrow Necrosis Inflammation by Free Fatty Acids Marrow Fat PE

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13 20/07/20 1

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15 Sickle Cell Disease: Multi-Organ Pathology Shortened Life Expectancy Stroke 24% of patients experience a stroke by age 45; 11% of patients experience a stroke by age 20 Acute Chest Syndrome occurs in 12% of SCD adults (leading cause of death) Kidney Failure Life expectancy of 1 yr. with dialysis Pain SCD patients experience pain 54% of days The New England Journal of Medicine, Volume 339, Issue 1 BJU International, Volume 90, Issue 9 Kidney International, Volume 57, Issue 1 Annals of Internal Medicine, Volume 4, Issue 2 The New England Journal of Medicine, Volume 350, Issue 9 Priapism Occurs in 35% of male patients and can result in erectile dysfunction or penile necrosis

16 Case 1: Female, 42 years old HbSS Lawyer, frequently abroad. No regular medication apart from contraceptive pill. Feels generally well but fatigue + Has not had a crisis for many years. Concerned: sister (also sickle cell disease) had a stroke aged 61 New onset headache Needs statement for travel insurance

17 Case 2: Male, 23 years old HbSS Student, active rugby player Compliant with folic acid, penicillin V, Vitamin D. > 5 hospital admissions for a painful crisis in last year Considers private arthroscopy Needs stronger pain killers

18 Some blood results: Haemoglobin g/l LOW Mean Cell Volume 94.5 fl Platelet Count 311 x10^9/l White Cell Count 10.1 x10^9/l Absolute Neutrophil count 7.2 x10^9/l Serum Creatinine 62 umol/l Total bilirubin 30 umol/l HI Haemoglobin 71.0 g/l LLOW Mean Cell Volume fl HI Platelet Count 243 x10^9/l White Cell Count 7.4 x10^9/l Absolute Neutrophil count 4.3 x10^9/l Reticulocyte count 23.0 x10^9/l HI Total bilirubin 51 umol/l HI

19 Discussion: Who are you must concerned about? What else do you need to know about these patients? What possible risks can you identify?

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22 Correlation Between Number of Crises and SCD Related Complications

23 The spectrum of sickle cell sub-phenotypes affected by hemolytic rate. Claudia R. Morris Haematologica 2011;96: by Ferrata Storti Foundation

24 Sickle Cell Related Symptoms Any new onset symptoms Observations Proteinuria Retinopathy Echocardiogram Vaccination status Iron overload Osteoporosis Counselling / family planning Annual Review (Similarities with Diabetes!)

25 Vaccination Scheme: Adults with sickle cell disease who have not received primary vaccination as part of the national schedule in the UK should be offered: One dose of HIB/Men C One dose of Men ACW&Y conjugate vaccine one month later Two primary doses of men B vaccine one month apart [this can be at the same visits as the other vaccinations above] A single 0.5 ml dose of pneumococcal conjugate vaccine (PCV13) [which should be given at least six months after pneumococcal polysaccharide vaccination (PPV23) if this has been previously administered] Adults with sickle cell disease should also be offered: Pneumococcal polysaccharide vaccination (PPV23) [given 6-12 months post PCV13] and at fiveyearly intervals thereafter. Annual influenza vaccination Hepatitis B vaccination if they have not previously received it and are non-immune (anti-hbs antibody titre < 100 miu/ml).

26 Options for prevention in SCD: Aims: Reducing number and intensity of painful crises Reducing long-term complications and organ damage. Means: Reduction of haemoglobin S percentage (experimental: reduce polymerisation) (experimental: reduce adhesion)

27 Reduction of haemoglobin S percentage (Exchange) transfusion Hydroxycarbamide (antimetabolite anti-cancer drug) increases foetal haemoglobin Bone marrow transplantation (experimental) phosphodiesterase inhibition

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29 (exchange) blood transfusion: Principle: Reduce those factors contributing to ongoing vicious cycle of hypoxia, HbS polymerisation, vaso-occlusions and then altered pulmonary flow. Reduce HbS percentage Avoid hyperviscosity (Hb 100 g/l) There is no evidence as to the optimal %HbS target post-exchange transfusion. In practice, a target of <30 40% is often used, but clinicians should be guided by the clinical response

30 Acute (exchange) blood transfusion: When: Exchange transfusion is indicated in the following circumstances: Acute neurovascular event Acute chest syndrome Clinical deterioration in pregnancy General deterioration due to a severe vaso-occlusive crisis requiring escalation of treatment/itu admission Sustained priapism refractory to routine management Acute, severely symptomatic anaemia (e.g., aplastic crisis) (If Hb < 60 simple top-up may also be used)

31 Acute (exchange) blood transfusion: In Acute Chest Syndrome Not all patients with ACS will require a blood transfusion Decision based on the degree of hypoxia and respiratory compromise. Prompt transfusion often results in a fairly rapid response as timing rather than target haemoglobin S% is important at this stage.

32 Indications for elective (exchange) blood transfusions: Secondary prophylaxis of acute vaso-occlusive crisis (stroke, acute chest syndrome, acute multiorgan failure) Surgery (preoperative transfusions) Pregnancy

33 Exchange blood transfusion: How: 1. Automated exchange transfusion (erythrocytapheresis) 2. Manual exchange transfusion

34 Manual exchange transfusion: Example: If Hb >.0g/dl Venesect 1 st unit WHILST Replacing with 500 mls of normal saline Venesect 2 nd unit THEN Transfuse 1st unit over minutes Venesect 3 rd unit THEN Transfuse 2nd unit over 1hour Venesect 4 th unit THEN Transfuse 3rd unit over 2 hours Check FBC and Hb S If Hb<9g/dl Transfuse 4 th and consider 5 th units (over 3 hours each) If Hb>9g/dl Restart from venesect 1 st unit

35 Sickle Cell specific transfusion-related challenges: Alloimmunisation rates are high, exacerbated by differences in blood group distribution between patients with SCD and the predominantly white European blood donor population. Alloimmunisation rates of up to 57% have been reported after 200 transfusions. The majority of alloantibodies are to RhD, RhC and Kell. A significant proportion of SCD patients have the Ro phenotype (cde) which is rare in donors of European origin. Serious Hazards of Transfusion (SHOT) reports show that transfusion reactions, especially acute or delayed haemolytic reactions, may be misinterpreted as sickle cell crises and treated inappropriately. As with thalassaemic patients, preventing alloimmunisation to Rh and Kell appears to reduce the development of antibodies to other blood groups. Extended blood group phenotyping is ideally carried out before the first transfusion. If patients have already been transfused, molecular typing can be used. Donor red cells should be sickle Hb negative, and ideally less than 14 days old for top-up transfusions and 7 days old for exchange transfusions. At a minimum, transfused red cells should be matched for ABO, D, C, E, c, e and Kell.

36 Back to Case 1: Female, 42 years old HbSS Lawyer, frequently abroad. No regular medication apart from contraceptive pill. Feels generally well but fatigue + Has not had a crisis for many years. Concerned: sister (also sickle cell disease) had a stroke aged 61 New onset headache Needs statement for travel insurance

37 Air travel

38 Flight Cabin Environment Cabin altitudes up to,000ft hypoxia gas expansion Reduced mobility Reduced humidity Circadian dysrhythmia Access to medications

39 Flying with SCD: UK CAA: Travel with supplemental oxygen Defer travel for approximately 10 days following a sickling crisis.

40 Back to Case 2: Male, 23 years old HbSS Student, active rugby player Compliant with folic acid, penicillin V, Vitamin D. > 5 hospital admissions for a painful crisis in last year Considers private arthroscopy Needs stronger painkillers

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42 Management of Painful VOC Acute pain Chronic pain

43 Management of acute sickle pain: NICE Principles Throughout an acute painful sickle cell episode, regard the patient (and/or their carer) as an expert in their condition Treat an acute painful sickle cell episode as an acute medical emergency and follow locally agreed protocols Offer analgesia within 30 min from presentation Do not use Pethidine

44 Treat as an emergency because?: Which of the following statements is true? 1. There is evidence that a timely intervention reduces the severity of the crisis and contributes to fewer long-term complications. 2. There is evidence that a timely intervention reduces the severity of the crisis and contributes to a shorter hospital admission or ED / day care treatment only. 3. There is evidence that early pain relief reduces stress. Stress can trigger or worsen a sickle cell crisis. 4. There is no evidence that a timely intervention is beneficial but a time-toanalgesia of < 30 minutes is internationally accepted as good clinical practice in severe pain and adapted by NICE guidance.

45 Barriers to effective pain management in sickle cell disease 1. Manifestation of vaso-occlusive pain Vaso-occlusive pain is complex and multifactorial. Primary etiology of acute episodic crises: vaso-occlusion of postcapillary venules. Most frequently boney areas where marrow is present. Children: hands, feet ( visible crises ) Adolescents and adults: many other etiologies: Avascular necrosis Regional pain syndromes Neuropathic pain Opioid-induced hyperalgesia Depression

46 Barriers to effective pain management in sickle cell disease 2. Negative provider attitudes Including perceptions that: People with SCD are addicted to opioids. 2-5% of SCD population are addicted to opioids Survey: 46% of ED providers believe >10% of SCD individuals addicted. SCD patients exaggerate their pain SCD patients are dishonest and manipulative SCD patients are uncooperative and frustrating to manage. Leading to..

47 Barriers to effective pain management in sickle cell disease Disrupted therapeutic relationship between patient and provider: SCD patients mistrust health care providers Leading to more stress Which is associated with more pain SCD patients often take an opposing position Which in turn reinforces negative provider attitudes

48 Patient Never Taken Opiates Before or mild pain? Co-codamol 30/500 x2 QDS NSAIDS (Ibuprofen 400mg) Not if urine dip +ve for protein/ low egfr/pregnant Oramorph 10mg PRN Max 3 doses in 4 hours if >40mg in 24 hrs change to: o o o o Zomorph 20mg BD & Oramorph 10mg PRN 6hourly OR Oxycontin 10mg BD & Oxynorm 5mg PRN 4 hourly

49 Possible strategies to improve patient management beyond the first dose: Individualised Care Plans Responsibility of SCD expert Based on home opioid consumption and what worked well previously Reduction of long-term opioid use Reduces tolerance; may achieve pain relief in the acute setting with fewer doses of opioids Croydon policy: no morphine TTA Patient-controlled analgesia: PCA promising strategy to safely provide repeat doses without straining available ED resources.

50 Case 3: Male, 1 years old Frequent crises and priapism as a child. Last few years relatively unremarkable. Heart rate 100/min, oxygen saturation 93% Mother is concerned because he looks pale and wonders if he needs iron Haemoglobin Mean Cell Volume Platelet Count Total bilirubin Lactate dehydrogenase Ferritin Assay 77.0 g/l LLOW 72.3 fl LOW 520 x10^9/l HI HI 3 umol/l HI (Unauth) 370 u/l HI (Unauth) 24 ug/l LOW

51 Sickle Cell Anaemia Causes of steady state anaemia: Haemolysis Reduced oxygen affinity leading to reduced erythropoietic drive Causes of worsening of anaemia: Splenic, hepatic or pulmonary sequestration Hypersplenism (usually only in infants and children) Parvovirus B19 infection Suppression of erythropoiesis in other infections Megaloblastic anaemia resulting from folic acid deficiency Iron deficiency Bone marrow infarction Hyperhaemolysis following blood transfusion Renal failure 20/07/20 1

52 Iron Deficiency in SCD Ferritin not most reliable parameter (acute phase); < 30 indicative SCD is not an iron-loading anaemia The usual causes Intravascular haemolysis -> haemoglobinuria -> iron deficiency In patients > 50 years: further investigations

53 Protective effect of anaemia Iron Deficiency in SCD: Less is better! Possible decrease in the severity of haemolysis Decrease in the Mean Cell Haemoglobin Concentration (MCHC) seems to delay Hb polymerisation Suppletion only after careful consideration Even brief iron therapy could precipitate a crisis

54 Folic Acid deficiency in SCD

55 Key points: Infrequent crises low risk of organ damage Frequent crises in adults correlates with high mortality rate Systems review for early detection of complications Prompt pain relief fewer admissions Barriers in effective pain management Iron suppletion only with great caution

56 Thank you Any questions? Any volunteers to participate in the local MDM?