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Sickle Cell Crisis

Sickle Cell Anemia

Sickle cell crisis is a clinical complication of sickle cell disease and occurs commonly in adolescents and adults. This is also called as vaso-occlusive crisis.


Presentation

The manifestation of sickle cell disease usually occurs in early childhood. The most common symptom of SCD is sickle cell crisis. It occurs due to obstruction of blood circulation in microvascular bed by the sickled erythrocytes, resulting in ischemic injury to the affected tissues. 

Pain crisis is the most important clinical feature of SCD and responsible for highest numbers of hospital admissions among SCD patients. Nearly 50% of the patients suffer from pain crisis. A sickle cell crisis is frequently associated with fever, malaise and leukocytosis

The pain crisis usually starts abruptly. The duration of crisis may last between several hours and several days and again terminates as abruptly as it begins. Bone marrow infraction due to vaso-occlusion often causes bone pain. As the bone marrow activity has defined patterns in different age groups, the pain also follows those patterns. For example, in children aged less than 18 months, metatarsal and metacarpals are involved, presenting as dactylitis. As age increases, the pain tends to occur in the extremities of long bones. It may resemble as joint pain due to proximity to the joints as well as sympathetic effusion. During adolescence, the pain moves towards the vertebral bodies, mainly the lumber ones. Though these patterns are common presentation of pain crisis, there might be other pain presentations depending on the affected site. Pain affecting the long bones is usually bilateral and symmetrical. Recurrent episodes in same individual usually follow the same distribution [2] [3] [10].

Involvement of the abdomen may present as acute abdomen case [8]. Acute abdomen may occur due to infraction of intra-abdominal organs or referred pain from other sites. Abdominal pain may be accompanied by back or joint pain. Vomiting is also a common presentation of such abdominal pain [2] [3] [9]. Each pain crisis episode generally involves two or more sites.  

Repeated episodes in the spleen leads to infractions and auto-splenectomy which may predispose to life-threatening infections. The liver may also suffer from infarction leading to hepatic failure. Renal involvement causes papillary necrosis which causes isosthenuria (i.e. inability in concentrating urine).

Fatigue
  • Other symptoms that developed included fatigue, left-sided rib pain, and shortness of breath. The patient recalled being told that she had sickle cell trait but said that she never had a sickle cell crisis.[ncbi.nlm.nih.gov]
  • What treatments manage symptoms of fatigue and anemia? Fatigue is a common symptom in persons with sickle cell anemia. Sickle cell anemia causes a chronic form of anemia, which can lead to fatigue.[medicinenet.com]
  • The symptoms of sickle cell disease include abdo ... minal pain, bone pain, shortness of breath, delayed growth, fatigue, fever and chest pain. A bone marrow transplant may cure the disease; otherwise, treatment focuses on symptom management.[sharecare.com]
  • People who have sickle cell disease may also have trouble coping with pain and fatigue, as well as with frequent medical visits and hospitalizations.[nhlbi.nih.gov]
Pallor
  • Pallor. First aid treatment for a sickle cell crisis Provide reassurance Contact medical help - the patient may know the details of who to contact during a crisis.[firstaidforfree.com]
  • General sickle crisis management Assessment History Symptoms and duration of pain, dyspnoea, fever, pallor and lethargy Provoking factors (fever, travel, procedures, recent hospital admission) Past history of chest crises and management - ICU admission[rch.org.au]
  • C) Difficulty breathing Chest pain Seizure Severe headaches Swelling in the abdomen (belly) Sudden weakness Weakness on one side of the body Loss of feeling and movement A painful erection of the penis lasting more than 4 hours Pallor When to call your[mountnittany.org]
  • Anaemia, jaundice, pallor, lethargy, growth restriction and general weakness; the most common causes of anaemia are acute splenic sequestration, transient red cell aplasia, and hyperhaemolysis in patients with severe infection. [ 3 ] Increased susceptibility[patient.info]
Limb Pain
  • The major symptoms are anemia, periodic joint and limb pain and sometimes edema of the joints, chronic ulceration about the ankles, episodes of severe abdominal pain with vomiting, and abdominal distention.[medical-dictionary.thefreedictionary.com]
Abdominal Pain
  • Abdominal pain is quite common in sickle cell crisis, although the cause of abdominal pain is seldom determined and remains controversial.[ncbi.nlm.nih.gov]
  • The abdominal pain may also reflect an acute surgical abdomen.A patient presented with sickle cell crisis and abdominal pain; he had a periappendiceal abscess at the site of an appendiceal stump five months after appendectomy.[ncbi.nlm.nih.gov]
  • We recently saw a 12-year-old black boy with known sickle cell disease who had been seen many times for abdominal pain thought to be secondary to a vasoocclusive crisis.[ncbi.nlm.nih.gov]
Severe Abdominal Pain
  • Go to a hospital's emergency department if these conditions develop: Uncontrollable pain even with the use of narcotics Continued loss of fluid leading to dehydration (if vomiting) Uncontrollable fever Chest pain or shortness of breath Severe abdominal[emedicinehealth.com]
  • The major symptoms are anemia, periodic joint and limb pain and sometimes edema of the joints, chronic ulceration about the ankles, episodes of severe abdominal pain with vomiting, and abdominal distention.[medical-dictionary.thefreedictionary.com]
  • Other serious warning signs that signal a need for immediate medical treatment are: Pain that doesn’t go away with home treatment Severe abdominal pain (stomachache) or swollen belly Chest pain Sudden vision problems Headache that’s different from usual[med.umich.edu]
Acute Abdomen
  • Involvement of the abdomen may present as acute abdomen case. Acute abdomen may occur due to infraction of intra-abdominal organs or referred pain from other sites. Abdominal pain may be accompanied by back or joint pain.[symptoma.com]
Periodontitis
  • Two cases of sickle cell crisis precipitated by periodontal infection are presented.[ncbi.nlm.nih.gov]
Chest Pain
  • In patients with SCD presenting to the emergency department with chest pain, it is important to consider non-SCD-related conditions, such as pulmonary embolus, before attributing pain to SCD.[emlyceum.com]
  • The symptoms of sickle cell disease include abdo ... minal pain, bone pain, shortness of breath, delayed growth, fatigue, fever and chest pain. A bone marrow transplant may cure the disease; otherwise, treatment focuses on symptom management.[sharecare.com]
  • Chest pain and hypoxaemia may be the only signs. Chest pain should be treated as an acute chest syndrome and not simply as a vaso-occlusive crisis.[rch.org.au]
  • pain acute splenic sequestration — typically occurs in infants — associated with increased spleen size — fall in Hb by 20 g/L, thrombocytopenia but normal or increased reticulocytes aplastic crisis — fall in Hb as well as reticulocyes — triggered by[lifeinthefastlane.com]
Hip Pain
  • pain for the past two years.[orthobullets.com]
  • If avascular necrosis of the hip is suspected in a patient with hip pain and difficulty in walking, consult an orthopedist for possible hip joint replacement. Orthopedic consultation is also appropriate if osteomyelitis is suspected.[emedicine.medscape.com]
Somnolence
  • The analgesics should not be discontinued automatically for somnolence as long as the patient is easily aroused. A common misconception is that if a person is sleeping, the analgesics are controlling the pain.[sickle.bwh.harvard.edu]
Neglect
  • The study illustrates that the present sample of nurses contributed to the poor pain control of sickle-cell patients because of their misconceptions about narcotic addiction, inadequate formal pain assessment and their neglect of attention to the psychosocial[ncbi.nlm.nih.gov]
Paresthesia
  • Two individual cases in which mental nerve paresthesia developed concurrently with sickle-cell crisis are described. A brief review of the hemoglobinopathies follows, with genetic considerations and clinical manifestations discussed.[ncbi.nlm.nih.gov]

Workup

The investigation of a patient with vaso-occlusive crisis should include a complete medical history, physical examination, selected laboratory workups and searching for precipitating factors which initiate the crises. The clinicians must examine for clinical evidence of associated infection and dehydration. The extent to which bone and soft tissues are affected should also be scrutinized. 

In patients with severe symptoms the laboratory tests should include complete blood count, urine analysis and reticulocyte count. If the patient is presented with fever, then an X-ray chest should be carried out along with culture of urine, sputum and blood to find out the possible source of infection. However, fever is a common symptom even in patients with uncomplicated vaso-occlusive crisis and therefore fever does not always indicate the presence of associated infection [3]. Painful crisis without bone marrow aplasia usually have increased count of white blood cells, often shifting to the left. This scenario is particularly found in case of bacterial infection. Platelet count also tends to increase.

In patients presenting with chest pain and/or difficulty in breathing, an acute chest syndrome or pulmonary embolism should be considered; hence chest radiograph and pulse oximetry are needed to exclude these differential diagnosis. 

Heinz Bodies
  • None of these patients presented with the classical “coca-cola” coloured urine or presence of Heinz bodies on reticulocyte preparations that are so characteristic of this condition.[adc.bmj.com]
Liver Biopsy
  • Transjugular liver biopsy showed focal areas of confluent necrosis and large areas of collapse. Cocaine intoxication should be considered in the differential diagnosis of hepatic failure in patients with sickle cell anemia.[ncbi.nlm.nih.gov]

Treatment

Most pain related to sickle cell disease can be treated with usual pain medications such as aspirin and ibuprofen. These can be found over the counter. In case of severe pain opioid (i.e. morphine) drugs  can be used along with routine pain medications. Some patients may be need hospital admission for severe pain.

 Acute pain crises are usually managed with drug therapy. Opioids like morphine are the drug of choice for such acute pain management. If necessary, paracetamol and NSAIDs can be used alongside opioids. Psychological support is very important in this regard. The standard treatment protocol includes opioid analgesics, rest, maintaining adequate hydration and cognitive-behavioral therapy [2]. There are several effective drug regimens for the treatment of pain crisis in SCD. Pain crisis management should follow the  “analgesic ladder” - a three step ladder approach recommended by the World Health Organization (WHO) for treating cancer-related pains [11].The choice of analgesic and the dosage schedule should  be based on pain severity and location.

Patients suffering from mild  pain can be treated at home by prescribing non-narcotic analgesics and oral fluid therapy [2] [12]. Acetaminophen can also be prescribed depending on the severity of pain. Non-steroidal anti-inflammatory drugs (NSAIDs) can also be used unless there are specific contraindications such as peptic ulcer disease (PUD), renal insufficiency or hepatic dysfunction.

Patients suffering from moderate to severe pain can be treated with narcotic analgesics. Effective pain management can be achieved through titration of dosage of the narcotic analgesics [1][2][12]. Usually morphine is given intravenously on hourly basis. Once the effective pain management occurs, then 3 hourly. Usually oral morphine is used in sustained release form after 24-48 hours after the pain is controlled. 

Severe pain episodes require emergency hospitalization. Stronger opioid analgesics are the drug of choice [6] [1] [2] [12] [13]. Though there are inconclusive findings about the efficacy of oxygen therapy in vaso-occlusive episodes, it is often used in managing such patients [13] [14].

Sickle cell crisis is often treated with adequate intravenous fluid administration and analgesics. Intravenous fluid management should be sufficient to correct ongoing dehydration and to replace fluid losses due to insensible loss and  fever. Usually normal saline and 5% DNS (i.e. dextrose in saline) are used to correct fluid balance. Dehydration may increase the plasma osmolarity and thus can worsen vaso-occlusive crisis through hemoglobin polymerization, intra-cellular dehydration and further sickling. The goal of fluid management is to maintian an euvolemic state.

In mild vaso-occlusive episodes, oral rehydration can be used. Parenteral administration is indicated in patients with vomiting, volume depletion and severe pain. In such cases, when existing volume deficits are corrected with normal saline, 5 percent DW (i.e. dextrose in water) or  25 percent normal saline [15]. In painful crises intravenous morphine is effective and safe; however meperidine is avoided.

Prognosis

Being a lifelong disease the prognosis of SCD is usually guarded. The main aim of management is to achieve a normal life span with minimal morbidity. Prognosis improves as the therapy improves. Aseptic necrosis may occur especially in weight bearing axis (e.g. femur) due to repeated infraction of bones, joints and growth plates. Such complication might lead to chronic disability requiring changes in lifestyle and employment. The economic loss and burden of disease soar up with such chronic pain. The frequency and duration of crisis, affected regions of the body and pain intensity affects patient's life quality [1]. 

Etiology

The prediction of vaso-occlusive crisis in sickle cell disease is quite difficult. In many patients, the exact cause of this crisis cannot be determined. However, dehydration, infection and cold weather are the common precipitating factors [1].

Factors that possibly cause sickle cell crisis:

Epidemiology

Sickle cell disease is a common problem in black population. The condition is also quite prevalent in the Middle East and Eastern Mediterranean regions. The estimated prevalence of sickle cell trait (i.e. heterozygous) is up to 30% in some parts of African region. SCD is also found in malaria endemic areas e.g. some parts of Greece, Sicily, southern Turkey and India. Epidemiological data has shown that around 5.2% of patients with sickle cell disease have 3 to 10 severe pain episodes every year [4], which usually resolve within 5 to 7 days in most of the patients. Though pain in severe episode may persists for weeks to months [1]. Patients with sickle beta 0-thalassemia and homozygous SCD suffer more from vaso-occlusive pain than patients with sickle beta(+)-thalassemia and hemoglobin SC [4] [5].

Sex distribution
Age distribution

Pathophysiology

Pain is the commonest complication of SCD. While travelling through the small blood vessels, the sickle cells obstruct small vessels, thereby hampering the blood flow. This results in sudden pain which can be mild to severe in nature and can last for different lengths of time. Acute exacerbation can occur intermittently; often for unknown causes. In some cases, viral infection, fever or local injury can precipitate the sickle cell crisis. 

Sickle cell crisis is mainly caused by ischemia and infraction of the affected area. Typically it occurs in the bones. Moreover, spleen, kidneys or lungs can be affected to a lesser extent. The crisis is initiated and maintained through the interactions among sickle cells, plasma constituents and endothelial cells  [6]. Occlusion of micro-vascular beds by sickle erythrocytes causes ischemic injury in the affected tissues. Occlusion of blood flow results in regional tissue hypoxemia and acidosis which leads to recurrent tissue injury and pain.  

On the other hand, chronic pain occurs due to destruction of bone tissues, joints and visceral organs as a consequence of recurrent injury done by crises. The unique pain syndrome occurs when unpredictable acute pain occurs on top of chronic pain [1] [7]. Severe pain symptom is probably resulting from increased intra-medullary pressure in the long bones, especially around the juxta-articular areas. This occurs as a result of acute inflammation and vascular necrosis of bone marrow tissue [3]. The pain originates from the involvement of periosteum or peri-articular soft tissues around the bone joints. 

Prevention

To prevent vaso-occlusive crises, patients should be aware of the precipitating factors for it. That's why patient education to recognize early signs of crisis is the cornerstone of prevention. Patients should seek help from the physician in case of fever or other imminent illness causing the crisis. Family members should also be educated on patient care such as hydration, diet, medication and immunization. Patients with SCD are susceptible to dehydration as they have decreased ability to conserve water. This occurs due to inability of kidneys to concentrate urine. Therefore, the patients should be advised to drink adequate water in hot weather and avoiding exercise at the point of eminent fatigue and dehydration. Patients are also advised to wear proper clothes depending on the environment to maintain normal core temperature. Regular follow up with blood counts should be carried out. Genetic counselling and testing is required for the patients as wells as asymptomatic heterozygous carriers. 

Summary

Vaso-occlusion in sickle cell disease (SCD) is responsible for wide variety of clinical complications such as sickle cell crisis, leg ulcers, stroke, renal insufficiency and spontaneous abortion. Among them, sickle cell crisis is the commonest one and is the main reason for emergency consultation in patients with SCD. Nearly half of the homozygous SCD patients suffer from vaso-occlusive crisis. However, its frequency is highly variable. 

Patient Information

Sickle cell disease (SCD) is a common inherited disease worldwide. Sickle cell crisis is the most common complication of SCD. Though in most patients, cause of this crisis is unknown, a number of factors can precipitate this condition such as infection, cold weather and dehydration [1]. The pain episodes are sudden in onset and gnawing and throbbing in nature. The skin of the affected region might be tender, warm, red and swollen. Recognizing pain crisis symptoms early and minimizing the precipitating factors are necessary to prevent such crisis. Patients are usually managed with adequate fluid management and transfusion of hemoglobin to decrease the level of hemoglobin S. The pain management is done by NSAIDs and opioid drugs. Family physician along with a hematologist should manage the patient to alleviate pain and prevent future crisis.

References

Article

  1. Shapiro BS. The management of pain in sickle cell disease. Pediatr Clin North Am. 1989;36:1029–45.
  2. Ballis SK, Carlos TM, Dampier C, and Guidelines Committee. Guidelines for standard of care of acute painful episodes in patients with sickle cell disease. Harrisburg, Pa.: Commonwealth of Pennsylvania Department of Health, 1996.
  3. Serjeant GR, Ceulaer CD, Lethbridge R, Morris J, Singhal A, Thomas PW. The painful crisis of homozygous sickle cell disease: clinical features. Br J Haematol. 1994;87:586–91.
  4. Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, et al. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991;325:11–6.
  5. Nagel RL. Sickle cell anemia is a multigene disease: sickle cell painful crises, a case in point. Am J Hematol. 1993;42:96–101.
  6. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340:1021–30.
  7. Payne R. Pain management in sickle cell disease. Ann N Y Acad Sci. 1989;565:189–206.
  8. Chiang EY, Frenette PS. Sickle cell vaso-occlusion. Hematol Oncol Clin North Am. 2005 Oct. 19(5):771-84, v.
  9. Ballas SK, Delengowski A. Pain measurement in hospitalized adults with sickle cell painful episodes. Ann Clin Lab Sci. 1993;23:358–61.
  10. Serjeant GR, Chalmers RM. Current concepts in haemotology. 1. Is the painful crisis of sickle cell disease a “steal” syndrome. J Clin Pathol. 1990;43:789–91.
  11. Cancer pain relief. Geneva: World Health Organization, 1986.
  12. Ballas SK. Management of sickle pain. Curr Opin Hematol. 1997;4:104–11.
  13. Zipursky A, Robieux IC, Brown EJ, Shaw D, O'Brodovich H, Kellner JD, et al. Oxygen therapy in sickle cell disease. Am J Pediatr Hematol Oncol. 1992;14:222–8.
  14. Schulman LL. Oxygen therapy in sickle-cell anemia [Letter]. N Engl J Med. 1984;311:1319–20.
  15. Okpala I. The management of crisis in sickle cell disease. Eur J Haematol. 1998;60:1–6.

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Last updated: 2018-06-22 05:00