Management of sickle cell disease in the communityBMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1765 (Published 10 March 2014) Cite this as: BMJ 2014;348:g1765
All rapid responses
The rapid response of Dr Konotey-Ahulu raises some disturbing thoughts.
Will the National Institute of Clinical Excellence please review its guidance? It may be that the published work of Dr Serjeant and that of Dr Konotey-Ahulu escaped the attention of the NICE researchers?
Competing interests: No competing interests
Management of Sickle Cell Disease in the Community: Role of Exercise
The latest BMJ Response surrounding articles of Brousse et al  and Liem et al  by Charlotte Greene, medical student at Kings College London  says Liem and colleagues “stress the importance of children and adults with sickle cell disease (SCD) being physically active.” She is “struck by the lack of advice and support for patients and their families in this area” even when “four recent studies of SCD patients showed no association between exercise and any adverse clinical event””, referencing Liem et al , Halphen at al , Liem et al , Karlson et al .
BUT EXERCISE IS BIG PRECIPITATING CAUSE OF SICKLE CELL CRISIS
Articles are flawed without specifying what “sickle cell disease” (coded SCD) stands for. My criticism  of Brousse et al  began: “Valentine Brousse and colleagues’ Clinical Review  gives doctors little guidance for patient management. ‘Serjeant’s and my combined experience of 80 years covering thousands of patients in sickle cell crisis’ can help”. . Majority of my 90 references are from Graham Serjeant and myself. We have supervised more sickle cell disease patients than anyone else in the world [8 9]. My largest ever Sickle Cell Clinic had records of more than 1,500 consecutive patients. [8 10]. Graham Serjeant and I managed two “SS” females from childhood to Oxford University without regular transfusion.
We criticised NICE Guidance on regular transfusion to maintain haemoglobin level of 11.0 gm/dL. Serjeant’s Hb SS never-been-transfused patient went on holiday in the USA, was transfused and died. .
We know exercise precipitates sickle cell crisis. We know Morphine and Diamorphine are dangerous for them. The NCEPOD REPORT [12 13] vindicates us for revealing “9 out of 19 patients with sickle cell disease who had pain on admission and who died had been given excessive dosage of opiods”. Sally Davies was asked last week: “Which unheralded change has made the most difference in your field?”  and she responded “Good pain relief can totally change the lives of people with sickle cell diseases” , without adding “although NCEPOD found that 9 out of 19 patients with sickle cell disease who had pain on admission and who died had been given excessive dosage of opiods”.
Serjeant and I know Hydroxyurea is anti-cancer drug. Patients have been “voting with their feet”  because of side effects “due to complications despite Hb F levels over 20%”? 
MY FAMILY EXPERIENCE
Three of my Trait parents’ 11 children suffered from sickle cell disease [8, page 11]. My younger brother with Sickle Cell Haemoglobin C disease from whose maxillary bone prominence I coined the word “gnathopathy” [8, p 178], was an excellent footballer. He would scream after midnight with sickle crisis pain having played football all afternoon. More than 70 years later Halphen and colleagues would confirm “severe nocturnal and post exercise hypoxia in children and adolescents with sickle cell disease”. 
I listed “Exercise” 54 years ago among 17 precipitating causes of sickle cell crisis. . Lactic acidosis from exercise and fluid loss from sweating provoke in vivo sickling. “Sicklaemic Human Hygrometers” are patients predicting heavy rainfall with onset of their sickle crises, a phenomenon I correlated with atmospheric vapour pressure variations.  Playing football those seasons was unwise.
RESEARCHERS MISTAKING SICKLE CELL TRAIT FOR SICKLE CELL DISEASE AND VICE VERSA
Sickle Cell TRAIT (“AS”) is often confused with Hb “SC” phenotype by being abbreviated to “SC Trait”. Sickle Cell Disease soldiers (“SC”) wrongly labelled “SC Traits” succumbed during rigorous exercises and were published as symptomatic Sickle Cell Traits [8 19]. Professor Hermann Lehmann published that Sickle Cell Traits won Olympic Gold Medals at Mexico City 7,000 ft above sea level. 
MODERATE EXERCISE HELPS IN PRIAPISM
Regarding priapism which usually begins after midnight I said: “Most patients could ‘abort’ an attack by getting up and walking about, jogging around the block or, in one case, cycling” [8, page 232] ensuring Pudendal artery compression. Rugby football risks ruptured spleen, and swimming killed my 10-year old patient..
GRAND ROUNDS AT KINGS COLLEGE HOSPITAL
When Professor of Medicine Kerry Mills supervised my Grand Rounds at KCH I took along a Ghanaian sickle cell disease “SC” businessman who has allowed me to name him (Ade Sawyerr). He explained during Question-Time that exercise produced his femoral-head aseptic necrosis shortening his leg, and how he refused Hydroxyurea, and Opiods for pain. He said: “I was diagnosed in Ghana aged 11 years by Dr Konotey-Ahulu when I was at Achimota School”. His “SC” had not stopped Ade Sawyerr achieving great things. Why should he now be told in London that Hydroxyurea would save his life? His eloquence and logic impressed everybody.
ADVICE TO MEDICAL STUDENTS
My 133 Illustrative Case Histories in “The Sickle Cell Disease Patient”. [8, pp 469-517] show that the patient is bigger than the disease. [22 23]. For example, a trait father with G6PD Deficiency and his sickle cell trait wife with Normal G6PD produced “SS” sons and daughters. The girls fared worse than the boys because only the former inherited their father’s G6PD Deficiency. I knew of only 3 UK Clinical Haematologists Professor Hermann Lehmann, Professor Lucio Luzzatto and Professor Sir David Weatherall all with whom I was on WHO Expert Advisory Committee on Human Genetics who would assay G6PD Enzyme for deficiency in their sickle cell disease patients. . G6PD Deficiency makes the patients worse. .
Finally, to pass exams medical students must reproduce what NICE recommends, remembering that Graham Serjeant and I disagree with NICE’s Guidance on regular blood transfusion, Hydroxyurea, Morphine and Diamorphine for sickle cell pain . On qualification, look for the many excellent UK General Practitioners who agree with Serjeant and myself. Learn from them, and your sickle cell disease patients will live long and become ACHIEVERS like Ade Sawyerr. Albert Einstein University College of Medicine’s Professor Helen Ranney published this: “There is no single clinical experience in the United States comparable to that of Dr Konotey-Ahulu”.
Competing Interest: Three of my siblings had sickle cell disease so I am quick to discern misleading information from experts. firstname.lastname@example.org
Felix I D Konotey-Ahulu FGA MB BS MD(Lond) DSc(UCC Hon) DSc(UH Hon) FRCP(Lond) FRCP(Glasg) DTMH(L’pool) FGCP FWACP FTWAS ORDER OF THE VOLTA (OFFICER) Kwegyir Aggrey Distinguished Professor of Human Genetics University of Cape Coast, Ghana; Former Consultant Physician Genetic Counsellor in Sickle Cell and Other Haemoglobinopathies Korle Bu Teaching Hospital & Director Ghana Institute of Clinical Genetics, and 9 Harley Street, Phoenix Hospital Group, London W1G 9AL. [Website: www.sicklecell.md ]
1 Brousse V, Vakali J, Rees DC. Management of sickle cell disease in the community. BMJ 2014; 348: g1765 doi:10.1136/bmj.g1765
2 Liem RI, Akinosun M, Muntz DS, Thompson AA. Feasibility and safety of home exercise training in children with sickle cell anemia. Pediatric blood and cancer, 64(12), pp.10.1002/pbc.26671. Epub 2017 June 9
3 Greene Charlotte. Management of sickle cell disease in the community. BMJ Rapid response 14 March 2019 http://www.bmj.com/content/348/bmj.g1765/rr
4 Halphen I, Elie C, Brousse V, Le Bourgeois M, Allali S, Bonnet D, De Montalembert M. 2014.Severe nocturnal and post exercise hypoxia in children and adolescents with sickle cell disease. Plos one. 9(5), pp. e97462.
5 Liem RI, Onyejekwe, K, Olszewski M, Nchekwuebe C, Zaldivar FP, Radom-Alzik S, Rodeghier MJ, Thompson AA. 2015. The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia. British Journal of Haematology, 171(5), pp 854-861.
6 Karlson CW, Baker AM, Bromberg MH, Elkin T, Majumdar S, Palermo TM, 2017. Daily Pain. Physical Activity, and Home Fluid Intake in Pediatric Sickle Cell Disease. Journal of Pediatric Psychology, 42(3), pp 335-344.
7 Konotey-Ahulu FID. Management of sickle cell disease in the community. BMJ Rapid Response BMJ 2014; 348: g1765 doi:10.1136/bmj.g1765 http://www.bmj.com/content/348/bmj.g1765/rr/694233
[with 90 references the majority by Graham Serjeant and FID Konotey-Ahulu]
8 Konotey-Ahulu FID. Konotey-Ahulu FID. The Sickle Cell Disease Patient: Clinico-Epidemiological Study of 1,550 consecutive patients at Korle Bu Hospital, Accra. Tetteh-A’Domeno Company [T-A’D Co], 1996 Reprint of 1991/92 Macmillan Press Ltd book. [643 pp] ISBN 0-951-5442-2-2-5http: www.sicklecell.md/aboutscd.asp
[King’s College Hospital’s Professor of Haematology Alastair J Bellingham MB FRCP FRCPath, London University, in Tropical Diseases Bulletin, 1993; Volume 90 No. 3, p 164: “This remarkable study must represent the largest compilation and report of a single person’s clinical experience … For professionals working within the community and hospital I can recommend it as a marvellous feast to delve into”] See also reference 26 of Professor Hen Ranney, New York, USA.
9 Serjeant GR, Serjeant B. Sickle Cell Disease, 3rd Edition Oxford University Press, Oxford 2001. [Seventeen more Graham Serjeant references from Jamaican experience listed under Reference 7 above]
10 Pattern of Sickle Cell Disease in Accra - A Study of 1,550 Consecutive Patients: A Thesis Presented 1971 for The Postgraduate Degree of Doctor of Medicine (MD) In University of London. [Awarded in 1972]
11 Serjeant GR. Blood transfusion in sickle cell disease. A cautionary tale. Lancet 2003; 361: 1659-1660. [Graham Serjeant’s adult never-been-transfused patient in Jamaica went on holiday in USA, was transfused and died.]
12 NCEPOD – National Confidential Enquiry into Patient Outcome and Death. SICKLE: A Sickle Crisis? 2008 [Sebastian Lucas (Clinical Coordinator),David Mason(Clinical Coordinator), M Mason (Chief Executive), D Wayman (Treasurer)/ Tom Treasurer (Chairman) email@example.com
13 Mason S. Enquiry shows poor care for patients with sickle cell disease. BMJ 2008; 336: 1152. “In 2 years 9 out of the 19 patients with sickle cell disease who had pain on admission and who then died had been given excessive doses of opiods”.
14 Konotey-Ahulu FID. Management of an acute painful sickle cell episode in hospital. NICE Guidance is frightening! BMJ Rapid Response September 7 2012. http://www.bmj.com/content/344/bmj.e4063/rr/599158
15 Davies Sally. BMJ CONFIDENTIAL. Sally Davies: Silk, noir, and diplomacy. BMJ 2019; 364:l1201 “Good pain relief can totally change the lives of people with sickle cell diseases” 23 March 2019 page 504.
16 Olujohungbe A, Cinkotai I, Yardumian A. Hydroxyurea therapy for sickle cell disease in Britain. BMJ Editorial 1998; 316: 1689. “Many patients are unwilling to take the drug …and voted with their feet.” [The late Dr Ade Olujohungbe was a Consultant Haematologist in the UK and Canada. He discontinued Hydroxyurea due to side-effects.
17 Kumar Neeta. Management of sickle cell disease in the community. Rapid Response 11 February 2017. http://www.bmj.com/content/348/g1765/rr “Two patients were reportedly succumbed to complication with SCD despite showing five-fold to ten-fold increase in Hbn F (5% to 25%, 3% to 31%)” Also quoting Vichinsky EP, Lubin BH. Blood 1994 Feb 15 83(4): 1124-8, and Ware RE, Eggleston B, Redding-Lallinger R, Wang WC, Smith-Whitley K, Daeschner C, Gee B, Style LA, Helms RW, Kinney TR, Ohene-Frempong K. Predictors of Fetal Haemoglobin response in children with sickle cell anemia receiving Hydroxyurea therapy. Blood 2002 Jan 1: 99(1): 10-4.
18 Konotey-Ahulu FID. Sicklaemic Human Hygrometers. Lancet 1965 May 8; 1(7393): 1003-1004 http://www.pubmedcentral.nih.gov/picender.fcg? [Listing precipitating causes of crises] artid=1846286&bloptype=pdf
19 Konotey-Ahulu FID. Beware of symptomatic sickle-cell traits. FID. Lancet 1992; 339(8792): 555. doi:10.1016/0140-6736(92)90377-F Feb 29. (Pointing out that the sickle cell trait ‘AS’ may not be true sickle trait, and the HbC trait ‘AC’ may be something else, as the "A" has been shown could stand for Hb Quebec-Chori, by Witkowska et al - New Engl J Med 1991; 325: 1150-54.)http://www.thelancet.com/journals/lancet/article/PII0140-6736(92)90377-F/fulltext Lancet [Also thoroughly explained in Reference 8 Chapter 30, pages 349 to 371].
20 Lehmann Hermann. Sickle Cell Trait. Olympic Athletes and Flying. The Times 1972. Letters to the Editor.
21…Bentsi-Enchill K, Konotey-Ahulu FID. Thirteen children from twelve pregnancies in sickle-cell thalassaemia. BMJ 1969; 3: 762 doi:10.1136/bmj.3.5673.762 [In Medical Memoranda Sept 27]. The 13th child of this remarkable D Family of Tema in Ghana can be seen on the lap of the mother in the family picture on the cover of the author’s book “The Sickle Cell Disease Patient” (Reference 8) visible on the Home Page of www.sicklecell.md He had sickle cell beta-Thalassaemia disease – S gene from father’s Sickle Cell Haemoglobin C (“SC”) disease and beta-Thalassaemia gene from mother’s sickle cell beta-Thalassaemia (“Sbeta-Thal”) disease. Warned when growing up never to swim in the sea, he disobeyed and was drowned at the age of 10 years swimming off Tema beach. This family is the only example in the world where father with hereditary Hb disease and wife also with hereditary Hb disease produced as many as 13 children all of them with Hb disease.
22 Konotey-Ahulu FID. Sickle-cell disease and the patient. Lancet 2005; 365(9457): 382-83 January 29-February 4. [Commenting on Marie Stuart & Ronald Nagel's "Sickle-cell disease” Seminar in Lancet 364: 1343-60, and Michaela Buckner's "Sickle-cell disease: from Sierra Leone to south-east London” Lancet 364: 1361, it is pointed out that "Stuart and Nagel missed something out of their Seminar, which Michaela emphasizes – circumstances”]
23 Konotey-Ahulu FID. Management of sickle cell disease versus management of the sickle cell disease patient. BMJ Rapid Response 17 September 2008. http://www.bmj.com/cgi/eletters/337/sep08_1/a1397#202088
24 Boyo Alex E, Cabannes R, Conley CR, Lehmann H, Luzzatto Lucio, Milner PF, Ringelhann B, Weatherall DJ, Barrai I, Konotey-Ahulu FID, Motulsky Arno G. WHO(Geneva) Scientific Group on Treatment of Haemoglobinopathies and Allied Disorders. (Technical Report) 1972: 509: 83 pages.
25 Acquaye CTA, KA Gbedemah, Konotey-Ahulu FID. Glucose-6-Phosphate Dehydrogenase Deficiency Incidence in sickle cell disease patients in Accra. Ghana Med J 1977; 16: 4-9. [D6PD Assay must always be done on sickle cell disease patients to prevent deterioration when certain drugs are prescribed].
26 Ranney Helen, In Sickle Cell Disease: Diagnosis, Management, Education and Research - Editors Harold Abramson, John F Bertles, Doris L Wethers. The C V Mosby Company Saint Louis. 1973, page 320. “There is no single clinical experience in the United States comparable to that of Dr Konotey-Ahulu” [See Professor Alastair Bellingham in Reference 8]
Patient consent received.
Competing interests: Three of my siblings had sickle cell disease so I am quick to discern misleading information from experts.
The authors stress the importance of children and adults with sickle cell disease (SCD) being physically active. Indeed, four recent studies of SCD patients ≤18 showed no association between exercise and any adverse clinical event (1-4). Yet, during my time undertaking a student selected module in paediatric haematology I was struck by the lack of advice and support patients and their families receive in this area.
The physical and mental health benefits of sport and physical exercise are well established and the NHS has published physical activity guidelines for children and young people. Physical activity and sport participation have been shown to protect against suicide and poor mental health in teenagers and improve their psychological wellbeing (5). Since children with SCD have the added psychological, educational and social burden of living with a chronic condition, it is surprising no guidelines exist for them (1).
More information and advice about physical activity is needed to provide paediatric SCD patients with true holistic care and improve their quality of life.
(1) LIEM, R.I., AKINOSUN, M., MUNTZ, D.S. and THOMPSON, A.A., 2017. Feasibility and safety of home exercise training in children with sickle cell anemia. Pediatric blood & cancer, 64(12), pp. 10.1002/pbc.26671. Epub 2017 Jun 9.
(2) HALPHEN, I., ELIE, C., BROUSSE, V., LE BOURGEOIS, M., ALLALI, S., BONNET, D. and DE MONTALEMBERT, M., 2014. Severe nocturnal and postexercise hypoxia in children and adolescents with sickle cell disease. PloS one, 9(5), pp. e97462.
(3) LIEM, R.I., ONYEJEKWE, K., OLSZEWSKI, M., NCHEKWUBE, C., ZALDIVAR, F.P., RADOM-AIZIK, S., RODEGHIER, M.J. and THOMPSON, A.A., 2015. The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia. British journal of haematology, 171(5), pp. 854-861
(4) KARLSON, C.W., BAKER, A.M., BROMBERG, M.H., DAVID ELKIN, T., MAJUMDAR, S. and PALERMO, T.M., 2017. Daily Pain, Physical Activity, and Home Fluid Intake in Pediatric Sickle Cell Disease. Journal of pediatric psychology, 42(3), pp. 335-344.
(5) TALIAFERRO, L.A., RIENZO, B.A., MILLER, M.D., PIGG, R.M.,JR and DODD, V.J., 2008. High school youth and suicide risk: exploring protection afforded through physical activity and sport participation. The Journal of school health, 78(10), pp. 545-553.
Competing interests: No competing interests
Author recommends prenatal screening in high risk or willing parents and neonatal screening of high-risk babies1. We would suggest an IN VITRO FERITLIZATION (IVF) and a preimplantation genetic diagnosis (PGD) in which after a screening of high risk or willing parents we find that both parents carry the genes (it is an autosomally recessive disease). If both parents are carriers then they would transmit the trait to 50% of their progeny, 25% will be affected and 25% would be healthy. We should select that embryo which is free of trait and implant it in mother's womb.
1. BMJ 2014;348:g1765
Competing interests: No competing interests
The article identifies future research areas such as the discovery and development of drugs designed to treat sickle cell disease, including those that promote haemoglobin F synthesis, prevent red cell dehydration, and inhibit HbS polymerization.
However working towards development of new drugs keeping these markers as target may be complete wrong direction. Currently used Hydroxyurea increases fetal hemoglobin (HbF) and improve the clinical course of sickle cell disease (SCD) patients. However, several issues of myelo-suppression, low WBC count and reticulocytes, low level of patient compliance ( due to cost or side effects), including differences in patients' drug clearance with hydroxyurea therapy remain unresolved, predictability of drug response, reversibility of sickle cell disease-related organ damage by hydroxyurea, and the efficacy of elevated HbF has been highlighted from practical observant . Two patients were reportedly succumbed to complication with SCD despite showing fivefold to tenfold increase in HbF (5% to 25%, 3% to 31%).
Clinicians have observed major SCD-related complications despite HbF levels over 20% hence suggest that the progressive vascular changes associated with SCD are unlikely to be dramatically affected by increased HbF levels . Ware et alii observed hydroxyurea-induced decreases in reticulocytes and WBC count, with rising %HbF at MTD. There may be transient action of reducing crisis with hydroxyuea use, That is why it is recommended in this article as emergency measure in crisis only, and in only those who had 2-3 episodes of crisis.
HbF as marker of efficiency has been proven inefficient in field situations; hence antisickling effect should eb the target of new drug development for SCD. Currently available drugs were developed using HbF as marker, however failure is evident by ground level situation of increasing mortality due to SCD .
In view of efficient role as anti-sickling phyto-medicines as upcoming promising therapies ( like Niprisan) which have shown potent anti- sickeling efficiency and prevention from crisis in RCTs, Cochrane review provide clue that even without affecting or giving rise in HbF or inefficient Hb, these phytomedicines may be boon for prevention and management of SCD.
i A cautionary note regarding hydroxyurea in sickle cell disease. Vichinsky EP1, Lubin BH. Blood. 1994 Feb 15;83(4):1124-8.
ii Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Ware RE, Eggleston B, Redding-Lallinger R, Wang WC, Smith-Whitley K,Daeschner C, Gee B, Styles LA, Helms RW, Kinney TR, Ohene-Frempong K. Blood. 2002 Jan 1;99(1):10-4.
iii Gujarat: 20% jump in deaths due to sickle-cell anaemia. http://indianexpress.com/article/cities/ahmedabad/gujarat-20-jump-in-dea...
iv Phytomedicines (medicines derived from plants) for sickle cell
disease (Review). The Cochrane Collaboration and published in The Cochrane Library
2015, Issue 4
Competing interests: No competing interests
Valentine Brousse and colleagues’ Clinical Review , gives doctors little guidance for patient management. “Serjeant’s and my combined experience of 80 years covering thousands of patients in sickle cell crisis” can help. .
DISAGREEMENT WITH NICE ON PATIENT MANAGEMENT
Graham Serjeant’s Jamaican experience  and my Ghanaian  differ from NICE’s Guidance  in UK where patients died from Morphine/Diamorphine overdose. [6 7] We managed sickle cell disease (scd) patients to university without Morphine/Diamorphine, Hydroxyuurea, or regular transfusions. Our experience (References 1965 to 2014} could save UK patients.
PROOF OF EXPERTISE http://bit.ly/1gDdMlN 
(1) Two brothers and one sister suffered from scd “Hereditary Rheumatism” traced back to 1670 AD www.konotey-ahulu.com/images/generation.jpg [9-11]. Siblings’ commonest cause of sickle cell crises characterized by convulsions and priapism [9 10] was Malaria. One brother had ‘gnathopathy’, my invented word for maxillary marrow hyperactivity [10 12 13 14].
(2) Directing largest Sickle Cell Clinic I catalogued 133 Illustrative Case Histories  including alcohol-induced myocardial infarction [10, p 503] and mental nerve neuropathy , kanumblll sign. Investigate any numb lower lip for scd. 
(3) Haematologist Helen Ranney published “There is no single clinical experience in the United States comparable to that of Dr Konotey-Ahulu” .
(4) Receiving with Linus Pauling and others “Martin Luther King Jr Foundation Award for Outstanding Research in Sickle Cell Anaemia” my Keynote Address “Difference between Sickle Cell Disease and Sickle Cell Trait” that exposed fraud of Insurance Companies led to being given 4 bodyguards in Philadelphia.  By saying Sickle Cell Trait was “largely asymptomatic”  Brousse et al repeated Insurance Companies’ misinformation/disinformation [18-21] used to levy Traits 150% Premium.
(5) On WHO Expert Genetics Advisory Panel with Haemoglobinopathy Greats who valued Ethics in Human Genetics. 
LESSONS FROM GRAHAM SERJEANT’S JAMAICAN EXPERIENCE
“In Jamaican experience morphia or its derivatives are rarely used or necessary”  and “the most painful crises may be treated in a day centre, the patient returning home in the evening” . See more of Serjeant’s publications from 1968 [23-38].
TIPS FROM MY FIRST PUBLICATIONS IN 1965 [39-41] TO LATEST 2014 [42 43]
(1) KEEP A DIARY! Circumstances [10 39], some patient-specific, precipitate crises eg Ghanaian scd man had sickle crisis on eating oranges . Would Grousse et al start Hydroxyurea  after twice eating oranges?
(2) ALWAYS CARRY UMBRELLA. One rain-soaked scd boy got sickle crisis and stroke . Trans-cranial Doppler  better prophylactic than raincoat? Hot weather too causes sickle crisis .
(3) NOSE PICKING causes Epistaxis [39 45].
(4) VALSALVA MANOEUVRE: In 18 causes of ocular bleeds  “six were related to sneezing, blowing nose, shouting, bending down, lifting heavy objects, and vigorous exercise” . Avoid Valsalva in labour; Caesarian Section advised.
(5) DOCTORS BEWARE! Ectopic pregnancy, gall stones , appendicitis, splenic infarct  misdiagnosed as “Abdominal crisis”. Squatting (Tourniquet effect) can start crisis . Opiates cause “Chest syndrome” . Pulmonary embolism missed . Note Intra-family scd phenotype differences [50 51]
(6) EXAMINE COMMUNITY RUMOUR. Medicated bed nets  no better than usual nets and may harm babies . Malaria kills scd patients quicker [10 53-55]. Patients shun Hydroxyurea [56 57] and prenatal diagnosis [58 59] Drinking up to 4 L of water a day has stopped crises for past 25 years, as has “Aerobic Oxygen” 20 drops tds in water  Coconut juice clearing jaundice? [60.]
(7) STATIONERY BICYCLE aborts early morning priapism [10, 43]
(8) PRE-SURGERY PARTIAL EXCHANGE TRANSFUSION (Bedside method) .
(9) GENETIC COUNSELLING & VOLUNTARY FAMILY SIZE LIMITATION [61-69]
(10) SICKLE CELL DISEASE PATIENT ACHIEVERS teach doctors 1993-2010 
(11) G6PD Deficiency: 1 in 4 male and 1 in 16 female scd patients have this. [71 72]
(12) WORLD SICKLE CELL DAY BROADCASTS AND RESOURCES [73 74]
WHAT CHOICE FOR UK CLINICIANS?
NCEPOD discovered “9 out of 19 patients with sickle cell disease who had pain on admission and who then died had been given excessive doses of opiods” [6 7]. Yet NICE still recommends “a strong opiod intravenously” . But Why? [2 4 10 48 75-87]. Patients complain to BMJ [88-90].
1 Brousse V, Makali J, Rees DC. Management of sickle cell disease in the community. BMJ 2014; 348:g1765 doi:10.1136/bmj.g1765
2 Konotey-Ahulu FID Opiates for sickle cell crisis? Lancet 1998: 351: 1438 “The question that puzzles me is why do west African and West Indian patients with sickle cell disease who did without morphine in our countries have to be given morphine pumps during sickle cell crisis when they come to the UK?”
3 Serjeant G. The case for dedicated sickle cell centres. BMJ 2007; 334: 477
4 Konotey-Ahulu FID. Dedicated sickle cell centres. BMJ Rapid responses March 20 2007 http://www.bmj.com/cgi/eletters/335/7618/462#167455
5 NICE GUIDELINES. Management of acute painful sickle cell episode in hospital; summary of NICE Guidance. BMJ 2012; 344: doi:http://dx.doiorg/10 1136/bmj’e’4063
6 NCEPOD - National Confidential Enquiry into Patient Outcome and Death. SICKLE: A Sickle Crisis? 2008 [Sebastian Lucas (Clinical Coordinator), David Mason (Clinical Coordinator), M Mason (Chief Executive), D Weyman (Researcher)/ Tom Treasurer (Chairman) firstname.lastname@example.org
7 Mason S. Enquiry shows poor care for patients with sickle cell disease. BMJ 2008; 336: 1152 “In 2 years 9 out of the 19 patients with sickle cell disease who had pain on admission and who then died had been given excessive doses of opiods”
8 Konotey-Ahulu FID. http://bit.ly/1gDdMlN International request to manage patients, for example, sicklecell.md/blog/index.php/2007/06/request-from-geneva-for-patient-in-hospital-in-colorado-usa June 2007
9 Konotey-Ahulu FID. Pattern of Sickle Cell Disease in Ghana (A Study Of 1,550 Consecutive Patients) – A Thesis Presented For The Degree of Doctor of Medicine (M.D.) In The University Of London 1971 Awarded Feb 1972.
10 Konotey-Ahulu FID. The Sickle Cell Disease Patient. Clinico-epidemiological study of 1550 consecutive patients at Korle Bu Hospital, Accra. T-A’D Co, Watford 1996 http://www.sicklecell.mde/aboutscd.asp
(Reprint of Konotey-Ahulu FID. The Sickle Cell Disease Patient. Natural History from a clinico-epidemiological study of the first 1550 patients of Korle Bu Hospital Sickle Cell Clinic. London & Basingstoke, Macmillan Press Ltd 1991/1992. Foreword by Roland B Scott MD, Howard Univ, Washington DC)
11 Konotey-Ahulu FID. Sickle Cell Disease In Successive Ghanaian Generations For Three Centuries (Manya Krobo Tribe) In The Human Genome Diversity Project: Cogitations of An African Native. Politics and The Life Sciences (PLS) 1999; Vol 18: No 2, pp 317-322.
12 Konotey-Ahulu FID. Effect of environment on sickle cell disease in West Africa; epidemiologic and clinical considerations. Chapter 3 in SICKLE CELL DISEASE – diagnosis, management, education and research. Eds Ahramson, Bertles JF, Wethers Doris L; St Louis – CV Mosby Co 1973, pp 20-38.
13 Konotey-Ahulu FID. The Sickle Cell Diseases: Clinical manifestations including the Sickle Crisis. Archives Intern Med 1974; 133: 611-619. http://archinte.ama.assn.org/cgi/reprint/133/4/611.pdf
14 Konotey-Ahulu FID. The liver in sickle cell disease. Clinical aspects. Ghana Med J 1969; 8: 104-118. (First ever use of word “Gnathopathy”)
15 Konotey-Ahulu FID. Mental nerve neuropathy: a complication of sickle cell crisis. Lancet 1972; 2: 388 [Constitutes discovery of a new physical sign in Clinical Medicine – The kanumblll sign spells out who discovered it, what it is, and where published: “konotey-ahulu numb lower lip Lancet” sign 1972]
16 Ranney Helen. Summary of Symposium 1972 on Sickle Cell Disease – Diagnosis, Management, Education and Research – In SICKLE CELL DISEASE, Eds H Abramson, John F Bertles, Doris Wethers (C Mosby Co), 1973, page 320: “There is no single clinical experience in the United States comparable to that of Dr Konotey-Ahulu”
17 Konotey-Ahulu FID. Four bodyguards and the perils of unmasking scientific truths www.bmj.com/cgi/reprint/335/7612/210.pdf BMJ 2007; 335: 210-11 BMJ July28 2007.
18 Konotey-Ahulu FID. Beware of symptomatic sickle cell traits. Lancet 1992; 339: 555. Doi:10.1016/0140-6736(92)90377-F (Pointing out that the Sickle Cell Trait ‘AS’ may not be true Sickle Trait, and that the Haemoglobin C Trait ‘AC’, may be something else, as the “A” has been shown could stand for Hb Quebec-Chori, by Witkowska et al - New Eng J Med 1991; 325: 1150-54 http://www.thelancet.com/journals/lancet/article/PII0140-6736(92)90377-F/fulltext
19 Konotey-Ahulu FID. Blaming sudden death on Sickle Cell Trait? Flaws in article of Charis Kepron, Gino Sobers, Michael Pollanen Exposed Sept 14 2011 www.sicklecell.md/blog/?p=105 or www.konotey-ahulu.com/blog/?p=105
20 Konotey-Ahulu FID. Sickle cell Trait Misinformation and Disinformation Nov 30 2011 www.sicklecell.md/blog/?=108 [Comprehensive Review]
21 Konotey-Ahulu FID. Further Communication on “Sickle Cell Trait Misinformation and Disinformation” and Sickle Cell Terminology: Disease or Disorder? www.sicklecell.md/blog/?p=127 April 16 2012
22 Boyo Alex E, Cabannes R, Conley CR, Lehmann H, Luzzatto L, Milner PF, Ringelhann B, Weatherall DJ, Barrai I, Konotey-Ahulu FID, Motulsky AG. WHO (Geneva) Scientific Group on Treatment of Haemoglobinopathies and Allied Disorders. (Technical Report) 1972; 509: 83 pages.
23 Serjeant GR. Sickle Cell Disease. Oxford, Oxford University Press, 1985.
24 Serjeant GR. Sickle cell disease. Lancet 1997; 35: 725-730.
25 Serjeant GR, Richards R., Barbor PRH, Milner PF. Relatively benign sickle cell anaemia in 60 patients aged over 30 in the West Indies. BMJ 1968; 3: 86
26 Serjeant GR, Serjeant BE, Milner PF. The irreversibly sickle cell: a determinant for haemolysis in sickle cell anaemia. Br J Haematol 1969; 17: 527-533.
27 Serjeant GR, Galloway RE, Gueri MC. Oral zinc sulphate in sickle cell ulcers. Lancet 1970; 2: 891
28 Serjeant GR. The clinical picture of sickle cell anaemia in Jamaica. MD Thesis, University of Cambridge, 1971.
29 Serjeant GR, Ashcroft. Shortening of the digits in sickle cell anaemia. A sequel of the hand-foot syndrome. Trop Gegraph Med 1971; 23: 341-346.
30 Serjeant GR, et al 1972. The conjunctival sign in sickle cell anaemia. JAMA 1972; 219: 1428-31
31 Serjeant GR, et al. The clinical features of sickle cell beta-thalassaemia in Jamaica. Brit J Haematolol 1973; 24: 19-30
32 Serjeant GR, et al. The clinical features of haemoglobin SC disease in Jamaica. Brit J Haematolol 1973; 24: 491-500.
33 Serjeant GR et al. Screening of cord blood for the detection of sickle cell disease in Jamaica. Clim Chem 1974; 20: 666-69.
34 Serjeant GR et al. The internal auditory canal and sensori-neural hearing loss in homozygous sickle cell disease. J Laryngol Otol 1975: 89: 453-455
35 Serjeant GR. Sickle Cell Disease, 2nd Ed. Oxford, Oxf Univ Press, 1992.
36 Serjeant GR, De Ceulaer C, Lethbridge R, et al. The painful crisis of homozygous sickle cell disease. Br J Haematol 1994; 87: 586-591.
37 Serjeant GR, Serjeant B. Sickle Cell Disease, 3rd Ed, Oxford, OUP, 2001.
38 Serjeant GR. Blood transfusion in sickle cell disease. A cautionary tale. Lancet 2003; 361: 1659-60 [Graham Serjeant’s adult not-transfused patient in Jamaica went on holiday in USA, was transfused and died!].
39 Konotey-Ahulu FID Konotey-Ahulu FID. Sicklaemic human hygrometers. Lancet 1965; 1:1003 1004 [Listing precipitating causes of crises eg hot weather etc] [http://www.pubmedcentral.nih.gov/picender.fcgi?artid=1846286&blobtype=pdf
40 Konotey-Ahulu FID. Torrential epistaxis associated with symmetrical facial skin ulceration in sickle cell anaemia. BMJ 1965; 2:859-860 doi:10.1136/bmj2.5466.859
41 Konotey-Ahulu FID, Kuma Eunice. Skeletal crumbling in sickle cell anaemia complicated by Salmonella typhi infection. Brit J Clin Practice 1965; 19: 575-578.
42 Konotey-Ahulu FID. Acute osteomyelitis in African children unmasks un-masks sickle cell disease with salmonellosis BMJ Rapid Response February 1 2014 http://www.bmj.com/content/348/bmj.g66?tab=response
43 Konotey-Ahulu FID. Erectile dysfunction: Test, please, for Sickle Cell Disease www.bmj.com/content/348.g129
44 Konotey-Ahulu FID. Sickle cell disease and the patient Lancet 2005; 382-383 Jan 29-Feb 4 [Importance of Circumstances in initiating crises]
45 Konotey-Ahulu FID. Epistaxis from sickle cell disease must not be forgotten www.bmj.com/content/344/bmj.e1097/rr/576087 28 March 2012
46 Konotey-Ahulu FID. Valsalva vitreous haemorrhage and retinopathy in sickle cell haemoglobin C disease. Lancet 1997; 349: 1774
47 Archampong EQ, Konotey-Ahulu FID. Biliary tract disease and sickle cell anaemia in Korle Bu Hospital, Accra. Ghana Med J 1975; 14: 176-180
48 Ringelhann Bela, Konotey-Ahulu FID. Haemoglobinopathies and Thalassaemias in Mediterranean areas and in West Africa: Historical and other perspectives 1910 to 1997. Accademia del Scienze Ferrara Atti, volume 74, Anno Accademico 174 1996-97, pages 297-307 [A Century Review]
49 Shoetan Cecilia. I lost my Sickle Cell Disease adult daughter minutes after being given Diamorphine intravenously when she could not breathe. http://www.bmj.com/cgi/eletters/336/7654/1152-a#196520 June 3 2008 BMJ
50 Konotey-Ahulu FID, Ringelhann B. Sickle cell anaemia, sickle cell thalassaemia, sickle cell haemoglobin C disease, and asymptomatic haemoglobin C thalassaemia in one Ghanaian family. BMJ 1969; 1: 607-612. http://www.bmj.com/cgi/reprint/2/5648/48.pdf [4 Hbnopathy phenotypes]
51 Konotey-Ahulu FID. Patterns of clinical haemoglobinopathy. East African Med J 1969; 46: 149-156 (With tables that distinguish phenotypes clinically)
52 The Globe and Mail, Toronto. Tough flights for mosquito nets. “If they are safe for babies and mothers in Africa, why are they not safe enough in Canada for a week?” 18 August 2006.
53 Konotey-Ahulu FID. Malaria and sickle cell disease. BMJ 1971; 2: 710-11.
54 Djabanor FFT, Reindorf CA, Konotey-Ahulu FID. The effect of sickle cell disease on Ghanaian children. In First International Publication No (HSM) 1974; 73-9141: 70-87
55 Konotey-Ahulu FID. Malaria and sickle cell: “Protection?” Or “No Protection?” – Confusion reigns. BMJ Rapid Response October 13 2008. http://www.bmj.com/cgi/eletters/337/oct01_3/a1875#203067
56 Olujohungbe A, Cinkotal I, Yardumian A. Hydroxyurea therapy for sickle cell disease in Britain. BMJ Editorial 1998; 316: 1689. “Many patients are unwilling to take the drug.”
57 Olujoungbe Ade. Bi-directional trust is needed in pain management in sickle cell disease. BMJ Rapid Response 2 July 1999 to Maxwell K, Streetly A, Bevan D BMJ 1999; 318: 1585-1590.
58 Konotey-Ahulu FID. Ethical issues in pre-natal diagnosis. BMJ 1984; 289: 185 http://www.bmj.com/cgi/reprint/289/6438/185-a.pdf
59 Konotey-Ahulu FID. Refusing to provide a pre-natal test for refusing later termination of pregnancy; can it ever be ethical? BMJ Rapid Response. November 20 2006 http://www.bmj.com/cgi/eletters/333/7577/1066#149662
60 Konotey-Ahulu FID. The Sickle Achievers (1). Ghanaian Times, July 23 2005 “I cannot think of a single Ghanaian family that did not have or know of someone with sickle cell disease – known by Tribal names”
61 Konotey-Ahulu FID. The Sickle Achievers (2) Ghanaian Times. August 13 2005 “Some time ago I coined the term for cold season Rheumatism which Europeans call Sickle Cell Disease … The ACHEACHE Syndrome (1 ACHE from each parent”. Makes it easy for Genetic Counselling.
62 Konotey-Ahulu FID. Genetic Counselling in sickle cell disease. BMJ 1969; 3: 235 http://www.bmj.com/cgi/reprint/3/5664/235.pdf (Put ‘ACHE’ for ‘BAD’) PERSONAL VIEW doi:10.1136/bmj.2.5648.48
63 Konotey-Ahulu FID. Sickle cell disease. The Case for Family Planning ASTAB Books Ltd, Accra, 1973
64 Konotey-Ahulu FID. Need for ethnic experts to tackle genetic public health. Lancet 2007; 370: 1836 [doi:10.1016/50140-6736(07)61771-1]
65 Ringelhann B, Konotey-Ahulu FID, Yawson G, Bruce-Tagoe AA, Miller A, Huisman THJ. Alpha Thalassaemia in West Africa. Symposium in Medical Genetics, Debrecen-Hajduszoboslo, Hungary (April 26-29 1976), pp 614-616 in Szabo G and Papp Z, Eds Medical Genetics, Excerpta Medica 1977
66 Konotey-Ahulu FID. Maintenance of high sickling rate in Africa: Role of polygamy. J Trop Med Hyg 1970 Jan; 73(1): 19-21 (38 References)
67 Bonney GE, Konotey-Ahulu FID. Polygamy and genetic equilibrium. Nature 1977; 265: 46-47 doi:10.1038/265046a0..n5589/pdf/265046a0.pdf
68 Konotey-Ahulu FID. Male procreative superiority index (MPSI): The missing co-efficient in African anthropogenetics. BMJ 1980; 291: 1700-02.
69 Konotey-Ahulu FID. The Male Procreative Superiority Index (MPSI): It’s relevance to genetical counselling. In FIFTY YEARS OF HUMAN GENETICS – A Festschrift and liber amicorium to celebrate the life and work of GEORGE ROBERT FRASER. Ed: Oliver Mayo & Carolyn Leach. Wakefield Press 2007, 1 The Parade West, Kent Town, Sth Australia www.wakefieldpress.com.au
70 Omaboe Letitia, Konotey-Ahulu FID. The Second International Conference on The Achievements of Sickle Cell Disease Patients. Accra 19th July 1995 Conference Brochure
71 Acquaye CTA, Gbedemah KA, Konotey-Ahulu FID. Glucose-6-phosphate Dehydrogenase Deficiency Incidence in Sickle Cell Disease patients in Accra. Ghana Med J 1977; 16: 4-9
72 Konotey-Ahulu FID. G6PD Deficiency in Ghanaians. How to recognise it.
Click ‘BLOG’ on www.sicklecell.md and click on January 2008 for 20 answers.
73 Konotey-Ahulu FID. WORLD SICKLE CELL DAY 19th June 2012 www.sicklecell.md/blog/?p=132 Featuring (i) The Inheritance of Sickle Cell Disease (ii) The Person with Sickle Cell Disease (iii) The Teenager with Sickle Cell Disease (iv) The Adult with Sickle Cell Disease.
74 WORLD SICKLE CELL DAY 19th June 1013. Broadcast Interview by Tunu Louise Roberts emphasising Public Health Approach to management, and Genetic Counselling with NORMACHE as Trait and ACHEACHE as Disease www.sicklecell.md or www.konotey-ahulu.com (Home Page) Also accessed as http://youtu.be/wEyebVIhr7Q [Suitable for patients and parents
75 Konotey-Ahulu FID. Morphine for painful crises in sickle cell disease. BMJ 1991; 302: 1604 (Commenting on Professor Chamberlain’s recommendation of morphine in pregnancy in sickle cell disease – BMJ 1991; 302: 1327-30). “In obstetrics what happens too foetal respiration when morphine is used?” http://www.bmj.com/cgi/reprint/302/6792/1604-c.pdf
76 Konotey-Ahulu FID. Management of patients with sickle cell disease. African Journal of Health Sciences 1998; 5: 47 [On Sally Davies and Lola Oni in BMJ 315: 656-60 “The Central Middlesex management protocol uses morphine infusions”] Response: “I fear Davies and Oni’s statement will make morphine the accepted drug for sickle crisis management. The consequences for such an approach are dire, especially when some UK hospitals are already making diamorphine their first choice”. And what did NCEPOD find in 2008?
77 Konotey-Ahulu FID. Opiates for sickle cell crisis. Lancet 1998; 352: 651-2
78 Konotey-Ahulu FID. Opiates for pain in dying patients and in those with sickle cell disease www.bmj.com/cgi/eletters/335/7622/685#177986 BMJ Response 11 Oct 2007
79 Konotey-Ahulu FID. Current “hit and miss” care provision for sickle cell disease patients in the UK. BMJ Rapid Response 16 July 2008. http://www.bmj.com/cgi/eletters/337/jul11_2/a/771#199135
80 Konotey-Ahulu FID. Management of sickle cell disease versus management of the sickle cell disease patient. BMJ Rapid Response 17 Sept 2008 http://www.bmj.com/cgi/eletters/337/sep08_1/a1397#202088
81 Konotey-Ahulu FID. Clinicians facing conflicting recommendations. Use common-sense? http://ww.bmj.com/cgi/eletters/337/nov28_2/a2530#205377 December 2008.
82 Konotey-Ahulu FID. Poor care for sickle cell disease patients: This wake-up call is overdue. BMJ Rapid Response (May 28) BMJ 2008; 336: 1152 http://www.bmj.com/cgi/eletters/336/7654/1152-a#196244 to Susan Mayor’s “Enquiry shows poor care for patients with sickle cell disease” on National Confidential Enquiry into Patient Outcome and Death (NCEPOD) REPORT “SICKLE: A Sickle Crisis? (2008)” http://email@example.com
83 Konotey-Ahulu FID. Inquest into diamorphine deaths: Does NCEPOD sickle cell patients report warrant a similar inquest? BMJ Rapid Response March 7 2009 http://www.bmj.com/cgi/eletters/338/mar03_3/b903#210208
84 Konotey-Ahulu FID. UK Drug related deaths are still rising: So where is NICE? http://www.bmj.com/cgi/eletters/sep01_1/b3536#219836 BMJ Rapid Response to S Mayor: “UK drug related deaths are still rising.” Sept 6 2009. .
85 Konotey-Ahulu FID. The politics and economics of pain relief in the West and Third World. http://www.bmj.com/cgi/eletters/341/aug11_2/c3800#240684 Response Aug 24 to T Anderson doi:10.1136/bmj.c3800 Aug 11 2010
86 Konotey-Ahulu FID. Management of an acute painful sickle cell episode in hospital. NICE Guidance is frightening! BMJ Rapid Response Sept 7 2012 www.bmj.com/content/344/bmj.e4063/rr/599158 (42 References)
87 Konotey-Ahulu FID. Opiods for chronic non-cancer pain – Chemotherapy – Clinical Guidelines: Where does ultimate responsibility lie? BMJ Rapid Response www.bmj.com/content/346/bmj.f2937/rr/651421 June 25 2013
88 Dankwa Akosua M. Sickle Cell patients deserve to live. BMJ Rapid Response to NCEPOD Report 11 July 2008 [Adult “SS” wrote to the BMJ:
http://www.bmj.com/cgi/eletters/336/7654/1152-a “I know 60 and 70 year olds (yes, sickle cell patients) who have got to that age without ever receiving this as treatment”.
89 Chapman Nyaho Mawunu. Poor care for the sickle cell disease patient: “Pain won’t kill him, but Morphine could”. BMJ Rapid Response to NCEPOD by adult Sickle cell haemoglobin C disease grand-mother 17 June 2008 http://www.bmj.com/cgi/eletters/336/7654/1152a
90 Amanor-Boadu Dorothy, Bruce-Tagoe Alexander, Konotey-Ahulu Felix. The Third International Conference On The Achievements Of Sickle Cell Disease (ACHEACHE) Patients, Accra – 19th July 2010. Adeko Ltd, Accra ISBN: 978-9988-1-3927-8 “One known ‘SS’ man with a PhD, who had never in his 63 years been transfused though Hb level was never above 8.8 g/dL and who had never been prescribed Hydroxyurea, astonished delegates when he announced ‘I do not remember when I last took a pain killer for my sickle cell anaemia. Drink plenty of water, avoid malaria, and have a positive attitude to life’” [page 15] Quoted in full in link of Reference 85 above. [Dorothy Amanor-Boadu herself is a 59-year old “SS” Nurse Oncologist in Accra].
Competing interests: Coming from a family with 3 Sickle Cell Disease (scd) siblings I find it very difficult to remain detached when the received wisdom in the management of scd patients that was proven by NCEPOD to be harmful is still endorsed by NICE.
The authors rightly describe that progesterone only contraceptives are safe in sickle cell disease. In addition, however, they should emphasise that not only are they safe, but that there is also good evidence that depot progesterone injections in particular can reduce the frequency of painful crises in sickle cell disease, and therefore represent a first line contraceptive in this group.
Competing interests: No competing interests