Episode 111: Sickle Cell Series - Acute Management of Sickle Cell Disease
In this week’s episode, we discuss the management of acute complications of sickle cell disease including acute pain episodes and acute chest syndrome as well as a discussion of hyperhemolytic syndrome.
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What is the workup for a patient with sickle cell disease presenting with an acute pain episode?
Complete blood count with differential
Type and screen (including an extended phenotype if new to the health care system)
Patients with chronic blood transfusions can have significant alloimmunization
Hemoglobin S percentage
Helpful as a baseline
Not the same as a Sickledex, which detects the presence of sickling hemoglobins and is used in newborn screening
Complete metabolic panel
Assess for existence of a pain plan, especially if the primary hematologist is from a different health care system
What is the optimal pain management for a patient with sickle cell disease presenting with an acute pain episode?
Can try oral pain medications but often these alone are not sufficient
If a pain plan is available, start with this
Often, patients may need to be started on a PCA (patient-controlled analgesia) pump
How are PCA settings determined?
If no pain plan is available, one way to determine initial PCA settings is shown below:
Review the patient’s home pain medication use and estimate the patient’s prior 24 hour pain medication usage
Take two thirds of that total amount and convert it to the preferred agent of choice (IV morphine or hydromorphone), then divide by 24 to get an hourly infusion rate
If this is less than or equal to 0.1 mg of hydromorphone per hour, start the PCA without any basal rate and use demand doses only
Considering using a loading dose as it can take a while to get the patient up to speed in terms of pain control utilizing demand doses alone
It is essential to reassess the patient after a couple of hours on these settings to see if they are working well and to assess for side effects, like itching and nausea
What is one example of the above method?
Consider a patient who uses Norco (hydrocodone-acetaminophen) 10-325 q4h PRN and has been mostly maxing out her home dosing, taking 5 tablets over the past 24 hr. She received a dose of hydromorphone 2 mg IV in the ED that provided substantial relief, but it only lasted for about an hour and a half before her pain was back at 9/10
Taking her 24 hour use of hydrocodone of 50 mg, that equates to about 3 mg IV hydromorphone over a 24 hour period. Divided by 24 hours, that’s about 0.1mg/hr, so a basal rate should be deferred for now
The 2 mg of IV hydromorphone she received worked well, and lasted around 90 minutes. A 15 minute dosing interval for demand doses is reasonable and allows leeway to increase or decrease the interval by 5 minutes based on how the patient is doing. 90 minutes of response equates to six demand doses at 15 minute intervals, and 2 mg divided by six demand doses is 0.33 mg/dose. This can be rounded up as the patient will be controlling her own doses and is not on a basal infusion rate that could accumulate and place her at risk for oversedation. Thus, 0.4 mg every 15 minutes can be used as the initial demand settings.
One way to calculate the loading dose is to triple the demand dose, capped at 2 mg. In this case, that equates to a loading dose of 1.2 mg of hydromorphone
Other than pain control, what are some other considerations?
It is important to maintain high oxygen saturations (at least 95%). Increasing the partial pressure of oxygen can help reduce the sickling process (recall from the first episode that HbS only polymerizes in the deoxygenated state).
Maintain hydration with IV fluids as tolerated by volume status. Be mindful of fluid overload in patients with heart failure, chronic kidney disease, and/or pulmonary hypertension
Encourage the use of adjunct pain medications like acetaminophen or ketorolac if kidney function permits. Also consider heating pads and muscle relaxants, particularly if these have been helpful in the past
Utilize an incentive spirometer. Ensure the patient has one at bedside and encourage frequent use to avoid atelectasis, as this can precipitate acute chest syndrome
How is acute chest syndrome diagnosed?
First, send a hemoglobin S level. If exchange transfusion is required, this information is necessary so this test should not be delayed
The first diagnostic criterion is a new pulmonary opacity involving one or more complete lung segments
The other is one of the following criteria:
Temperature greater than 38.5° C (64% of adults will have this)
At least 3% decrease from baseline O2 saturation
Tachypnea
Visibly effortful respiration (retractions, nasal flaring, accessory muscle use)
Cough
Wheezing
Rales / crackles
Chest pain (84% of adults present with this)
Overall, the spectrum of presentations can be broad, ranging from mild chest pain precipitated by a viral infection, to severe acute chest syndrome which can progress rapidly and is immediately life threatening.
What is the management of a mild presentation of acute chest syndrome?
The most common presentation of acute chest syndrome is mild, such as a patient presenting to the emergency department with a fever, a faint new opacities on chest X-ray, and a low-normal oxygen saturation on room air
In such patients without a history of severe acute chest syndrome requiring exchange transfusion, it is reasonable to start with 1-2 units of simple packed red blood cell transfusion, administration of supplemental oxygen to maintain oxygen saturation > 95%, and empiric antibiotic coverage for community acquired pneumonia
Remember to get a repeat HbS level after transfusion, in case exchange transfusion is required
What is simple vs exchange transfusion?
A simple transfusion is administration of packed red blood cells, which will restore normal hemoglobin and dilute hemoglobin S levels
An exchange transfusion involves drawing out the patient’s blood and replacing it with normal packed red blood cells. This requires a large-bore line for access as well as the assistance of the blood bank / transfusion medicine department
Exchange transfusion can help avoid some of the complications of excessive blood transfusions, such as transfusion-associated cardiac overload (TACO) and transfusion-related acute lung injury (TRALI)
Which patients with severe acute chest syndrome require emergency exchange transfusion?
Patients with a history of severe acute chest syndrome requiring exchange
Patients with diffuse acute chest X-ray findings
Oxygenation continues to worsen despite simple transfusion
Hypoxemia is particularly severe (for example, below 85%)
Evidence of other organ systems being involved, especially multiorgan failure following. There is a possible association with declining platelet count at the time of presentation.
What are some other indications for emergency exchange transfusion in patients with sickle cell disease?
Patients with stroke or suspected stroke
Patients with multiorgan failure
Consider exchange transfusion if a patient on chronic exchange transfusions is admitted for another reason and is expected to remain admitted for an extended period of time, beyond when they would be due for exchange. This is case-specific and should be discussed with the primary hematologist and the blood bank
Do all patients with sickle cell disease require blood transfusion?
Excessive blood transfusions leads to alloimmunization, which can make it very difficult to prepare units of packed red blood cells in the future
In order to avoid this, blood transfusions should not be administered to patients with sickle cell disease who do not have significant symptoms and are at their baseline hemoglobin
What is the etiology of worsening pain in acute chest syndrome?
This pain does repeat worsening vaso-occlusion
However, this pain can also represent bone marrow infarction and fat microemboli in the pulmonary circulation, which is thought to cause the most rapidly progressive form of acute chest syndrome
What is hyperhemolytic syndrome?
There is controversy about the existence of this, as it can be considered a type of delayed hemolytic transfusion reaction that presents with brisk hemolysis
This often presents with severe back pain, hemoglobinuria, and acute drop in hemoglobin
The central idea is “bystander” hemolysis - that is, a transfused unit of blood causes a degree of hemolysis, which then leads to more significant hemolysis due to a hyper-activated immune system
What is the management of hyperhemolytic syndrome / brisk hemolysis?
Management includes supportive blood transfusions and repeating type and screen to assess for new red cell antibodies as part of transfusion reaction workup. Recall that delayed hemolytic transfusion reactions are due to antibodies against minor red cell antigens
In severe presentations, patients can be given intravenous immune globulin (IVIG) and steroids to help reduce hemolysis
What is a splenic sequestration crisis?
In patients with residual splenic function (especially those with non-HbSS genotypes, such as HbSC) patients can develop a “splenic sequestration crisis”
Recall that the spleen is typically non-functional by adulthood due to chronic infarction throughout early life
Splenic sequestration is characterized by a constellation of findings:
Acute drop in hemoglobin of at least 2 g/dL below baseline
Splenic enlargement on exam, often firm and painful
Drop in platelet count (spleen sequesters platelets, not just red blood cells)
Reticulocytosis (compensation for acute anemia)
Patients can develop hypovolemic shock from hemorrhaging into their spleen
What is the management of splenic sequestration?
Management is complex and requires a delicate balance between supporting hemodynamics and perfusion while also being judicious with transfusions
Once the crisis resolves, the patient will frequently “auto-transfuse” all the sequestered red cells back into circulation, which can lead to hyperviscosity if the patient has been transfused excessively
Start by supporting hemodynamics with IV fluids
For patients with persistent symptomatic anemia, consider cautious transfusion, generally administering half of what might normally be given based on degree of anemia
If the patient’s hemoglobin rises above 11 g/dL, consider therapeutic phlebotomy with IV fluid replacement to avoid hyperviscosity complications such as stroke and cardiopulmonary issues
After the crisis abates, patients are recommended to undergo elective splenectomy in order to avoid recurrence in the future
A similar phenomenon can happen in the liver as well, known as acute hepatic sequestration, and with similar precautions about hyperviscosity. These episodes typically cause less hemodynamic compromise, but can still be quite concerning. Management considerations are similar to splenic sequestration, with hemodynamic and perfusion support, although patients can usually be started on simple transfusion instead of crystalloid resuscitation. Again, the CBC should be closely monitored as the crisis resolves.
What are the take home points?
Manage pain aggressively and check in frequently on patients to ensure a balance between pain control and side effects like oversedation, itching, and nausea
Acute chest syndrome is a true hematologic emergency, but it comes in a spectrum of severity that has to be managed in different ways
Inpatient emergent exchange transfusions are a vital intervention for acute stroke, severe acute chest, and multiorgan failure
Acute onset anemia should raise concern for the possibility of a delayed hemolytic transfusion reaction / hyperhemolysis syndrome and splenic or hepatic sequestration
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References:
Chaturvedi S, Ghafuri DL, Glassberg J, Kassim AA, Rodeghier M, DeBaun MR. Rapidly progressive acute chest syndrome in individuals with sickle cell anemia: a distinct acute chest syndrome phenotype. Am J Hematol. 2016 Dec;91(12):1185-1190. doi: 10.1002/ajh.24539. Epub 2016 Oct 3. PMID: 27543812.
Emond AM, Collis R, Darvill D, Higgs DR, Maude GH, Serjeant GR. Acute splenic sequestration in homozygous sickle cell disease: natural history and management. J Pediatr. 1985 Aug;107(2):201-6. doi: 10.1016/s0022-3476(85)80125-6. PMID: 4020541.
Hassell KL, Eckman JR, Lane PA. Acute multiorgan failure syndrome: a potentially catastrophic complication of severe sickle cell pain episodes. Am J Med. 1994 Feb;96(2):155-62. doi: 10.1016/0002-9343(94)90136-8. PMID: 8109600.
Hulbert ML, Scothorn DJ, Panepinto JA, Scott JP, Buchanan GR, Sarnaik S, Fallon R, Chu JY, Wang W, Casella JF, Resar L, Berman B, Adamkiewicz T, Hsu LL, Smith-Whitley K, Mahoney D, Woods G, Watanabe M, DeBaun MR. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia. J Pediatr. 2006 Nov;149(5):710-2. doi: 10.1016/j.jpeds.2006.06.037. PMID: 17095350.
Vichinsky EP, Styles LA, Colangelo LH, Wright EC, Castro O, Nickerson B. Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative Study of Sickle Cell Disease. Blood. 1997 Mar 1;89(5):1787-92. PMID: 9057664.
Win N, Sinha S, Lee E, Mills W. Treatment with intravenous immunoglobulin and steroids may correct severe anemia in hyperhemolytic transfusion reactions: case report and literature review. Transfus Med Rev. 2010 Jan;24(1):64-7. doi: 10.1016/j.tmrv.2009.09.006. PMID: 19962576.
The crew behind the magic:
Show outline: Ronak Mistry
Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath
Editing: Resonate Recordings
Shownotes: Neil Biswas
Social media management: Ronak Mistry
We are proud to partner with HemOnc.org!
Want to learn more about the trials that lead to the regimens discussed today? What about dosing schedules? See links in the show notes for a link to HemOnc.org
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