Sickle Cell Disease (SCD) is an inherited disorder that affects nearly 100,000 Americans. Since its discovery 101 years ago, SCD has fallen largely under the academic jurisdiction of hematology. Today, a small group of clinicians/researchers/scientists (mostly hematologists) works to add to the body of sickle cell literature
After evaluating this article, participants will be able to:
1. Incorporate an evidence-based approach into the care of patients with sickle cell disease
2. Improve clinical practice by addressing common misconceptions about management
3. Recognize and treat the complications of sickle cell disease more effectively
Sickle Cell Disease (SCD) is an inherited disorder of hemoglobin that affects nearly 100,000 Americans. Since its discovery 101 years ago, SCD has fallen largely under the academic jurisdiction of hematology. Today, a small group of clinicians/researchers/scientists (mostly hematologists) works to add to the body of sickle cell literature (a pubmed search for “sickle cell” returns less than 20,000 articles, compared to 120,000 for asthma and over 150,000 for CHF). Meanwhile outside of the ivory tower, SCD falls largely under the clinical jurisdiction of emergency medicine. SCD is marked by recurrent acute events (pain, stroke, acute chest syndrome), many of which result in an ED visit. While evidence to guide the emergency care of SCD patients is limited, there are several important points we can glean from the available literature. As one of very few emergency physicians with an interest in SCD, I’ve compiled a list of ten things I think every emergency practitioner should know.
Sickling is not the problem.
The traditional understanding of the pathophysiology underlying SCD was as follows: mutated hemoglobin causes red blood cells to take on a sickled shape in response to stress. These sickled cells then get stuck in small vessels and downstream ischemia leads to pain, stroke and other manifestations. This model has been replaced. A vastly oversimplified, but adequate explanation of the current understanding is that the manifestations of SCD are largely the result of abnormal cell adhesion (the blood is sticky) and endothelial dysfunction (blood vessels cannot vasodilate when they need to). While sickling may be the sentinel event, the ‘stickiness’ of the blood appears to be the result of inflammation and activation of cellular cascades within the blood (white blood cells, platelets, coagulation). There are several therapies in clinical trials that attempt to combat these processes.
Patients with high hemoglobin are more likely to have pain.
A common misconception is that painful episodes will usually be associated with a drop in hemoglobin. In fact, the opposite is true. Steady state hemoglobin values in patients with SCD can range from 3 to 14 mg/dL. Emerging data suggests that patients with higher baseline levels (typically above 8.5 mg/dL) have higher rates of vasoocclusive symptoms such as pain, stroke and acute chest syndrome. Patients with low hemoglobin levels tend to have less pain, but more pulmonary hypertension and skin ulcers. Regardless of the hemoglobin level, anyone with SCD can have pain and unfortunately, there is no objective test to ‘measure crisis.’ Laboratory tests (CBC, retic count, LDH, bilirubin) and vital signs have no utility in confirming or refuting whether a patient is actually having a painful episode. If the patient has SCD and they say they’re having pain, even if they look comfortable, you should believe them.
Hydration does not cure crisis, too much fluid may even be harmful.
It is common practice among EPs to give bolus isotonic crystalloid to SCD patients who present with painful episodes. Conversely, many hematologists believe that excess hydration is dangerous, and that all intravenous fluids given to SCD patients should be hypotonic (e.g. ½ NS or D5 ½ NS) and given at a maintenance rate. Excess hydration is associated with the development of atelectasis, and atelectasis is associated with the development of acute chest syndrome, a leading cause of death in people with SCD. Hypotonic fluids are recommended because they have been shown to reduce sickling in vitro and in vivo (unfortunately the effect of hypotonic fluid on clinical outcomes has not been studied). Based on this evidence, the expert consensus is that isotonic bolus fluids are appropriate when the patient is overtly hypovolemic (diarrhea or vomiting with hypotension, sepsis, etc). For pain crisis without hypovolemia, gentle hypotonic fluids (D5 ½ NS at maintenance) are recommended, and fluid overload should be avoided. For all admitted patients, an incentive spirometer is helpful to prevent atelectasis and the development of acute chest syndrome.
Creatinine does not reflect renal function in SCD patients.
Be gentle to their kidneys, use NSAIDs sparingly. Individuals with SCD develop progressive chronic renal insufficiency as their kidneys accumulate medullary infarcts. This steady and inevitable decline is not accurately reflected by the creatinine because SCD patients also have supranormal proximal tubule function. The clinical bottom line is that a patient with a creatinine of 1.0 mg/dL may be quite close to dialysis, and all nephrotoxic drugs should be avoided. Most relevant to the EP are NSAIDs and meperidine (Demerol). Meperidine is renally cleared and its metabolite, normeperidine, may accumulate in patients with renal dysfunction and cause neurotoxicity (seizures). NSAIDs are excellent analgesics, especially in combination with opiates, but they should be used sparingly. Acetaminophen and oral antihistamines can also have opiate sparing effects without the potential for renal damage. Reserve NSAID use for the most refractory cases of pain, and only after other opiate sparing medications have been given.
Administer supplemental oxygen only when patients are hypoxic.
Case report and anecdotal data suggest that supplemental oxygen suppresses bone marrow which can lead to transfusion in patients with SCD. Frequent transfusions predispose to the development of allo-antibodies which make it very difficult to find matching blood when transfusions are necessary. Similar to IV fluids, hypoxia may induce SCD crisis, but hyperoxia does not cure crisis. If the patient’s oxygen saturation is above 92%, supplemental oxygen is not recommended.
In children with SCD, the treatment for stroke is exchange transfusion.
In adults thrombolysis can be considered. Stroke is one of the most devastating complications of SCD. The age distribution of stroke in SCD is bimodal, with a peak in childhood (5-15) and a second peak after the age of 30. The pathophysiology of stroke in these two age groups is believed to be different (stroke in children is due primarily to the abnormal cell adhesion of SCD, while in adults the etiology is vascular disease – similar to the general population), thus the recommended treatment is different. In children with stroke, the treatment is emergent exchange transfusion to reduce the amount of abnormal hemoglobin below 30% and thrombolysis is contraindicated. In adult SCD patients with stroke, treatment should be the same as the general population (emergent neurology consultation and consideration of thrombolysis based on the duration and severity of symptoms). Diagnosis is very challenging in children with suspected TIA. In this situation, admission for urgent MRI/MRA is indicated. If the MRI shows evidence of cerebrovascular disease, the child is placed on a prophylactic regimen of chronic transfusions.
The treatment for ac
ute chest syndrome is exchange transfusion, a simple transfusion is adequate when exchange is unavailable.
Acute chest syndrome is a clinical entity marked by hypoxia, fever and pulmonary infiltrates. Many EPs are confused by this because the definition of acute chest syndrome is identical to the definition for pneumonia. There are essentially two reasons that acute chest syndrome is defined as a clinical entity separate from pneumonia: 1) it is not always caused by infection and 2) acute chest syndrome must be treated with exchange transfusion in addition to standard pneumonia therapy. Clinically, patients who respond well to standard pneumonia therapy are labeled as having pneumonia. Those who become progressively more hypoxic despite antibiotics and fluids are labeled as acute chest syndrome and will likely need exchange transfusion to save their life. In the event that exchange is not available, a simple red cell transfusion may be adequate.
Intraocular pressure measurement is mandatory for all eye trauma in patients with SCD and with Sickle Trait.
In individuals with SCD, hyphema (blood in the anterior chamber of the eye) can block drainage of aqueous humor from the anterior chamber of the eye. The result is acute narrow angle closure glaucoma, an immediate threat to vision. This phenomenon has even been described in SCD patients where the amount of blood in the anterior chamber was too small to be seen by the naked eye, as well as in individuals with sickle cell trait. Thus, in any SCD or trait patient who reports trauma to the eye, intraocular pressure measurement is essential. The threshold for ophthalmologic consultation and admission for serial intraocular pressure measurements should be very low.
SCD patients with transient red cell aplasia must be isolated from pregnant patients and healthcare workers.
Transient red cell aplasia (TRCA) is caused by infection with parvovirus B19, which causes red cell production to halt for 3-7 days. In normal individuals red cells live for approximately 90 days; thus, the brief cessation in red cell production causes no symptoms. Individuals with SCD have faster red cell turnover, and parvovirus infection can cause a precipitous drop in hemoglobin levels. The EP should suspect parvovirus infection when a drop in hemoglobin is noted with a low reticulocyte count, which indicates an inappropriate lack of red cell production.
Parvovirus antibody testing is not useful for rapid diagnosis. The critical action for the EP is to recognize the infection (low hemoglobin and low reticulocyte count) and isolate the patient immediately from pregnant patients and healthcare workers (Parvovirus infection during pregnancy is associated with fetal hydrops and stillbirth). Once the patient is isolated, a hematology consultant can inform the decision to initiate treatment with IVIG infusion.
Sickle cell pain crisis is a diagnosis of exclusion.
Patients with SCD are also at risk for diseases that affect the rest of the population. Always formulate a differential diagnosis. For example, in the SCD patient with right lower quadrant pain, consider appendicitis, ovarian torsion, pelvic inflammatory disease and kidney stone before simple pain crisis. When managing pain, use opiates aggressively and base the dosage on the patients home opiate usage whenever possible. Higher opiate doses up front will result in less opiate administration overall. Be compassionate and non-judgemental.
Emergency management of SCD patients can be both challenging and rewarding. With these principals in mind, anyone can provide exceptional care to people with SCD.