Hematologic Emergencies in the Critical Care Setting Part 2

Background: Hematologic emergencies in the critical care setting are rare but deadly complications that can often be managed appropriately if identified early on and received prompt intervention. In this 2-part review, we will discuss several hematologic emergencies and discuss the literature on current guidelines and principles of management.

Shoon Oo MD1 , Vinh Dao MD1, Kenneth Snell MD2, David Goldenberg DO2, Frank Lodeserto MD3

1. Department of Internal Medicine, Cape Fear Valley Medical Center, Fayetteville, North Carolina
2. Department of Anesthesiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
3. Department of Critical Care, Cape Fear Valley Medical Center, Fayetteville, North Carolina

Acute Chest Syndrome

Acute chest syndrome (ACS) is a leading cause of hospitalization and mortality in both pediatric and adult patients afflicted by Sickle Cell Disease. It can occur in any sickle cell phenotype, most common in HbSS1. The most likely etiology is due to vaso-occlusive crisis (VOC), characterized by bone marrow ischemia and necrosis resulting in the release of particles (Combination of bone marrow and fat). These particles travel to the lungs triggering ACS2. The most common risk factors include infection, dehydration, the presence of hyperactive lung disease, surgery, trauma, and smoking. ACS is defined by a new pulmonary density on chest imaging involving at least one complete lung segment and at least one of the following: fever 38.5C, 2% or greater decrease in SpO2 from steady state documented room air, and signs of respiratory distress3. Distinguishing the difference between ACS and pneumonia based on signs, symptoms, and radiographical studies is difficult, however, the mortality caused by both etiologies is high, and empiric treatment for both should be initially considered until elucidated.

Basic labs such as complete blood count (CBC), complete metabolic panel (CMP), type and screen for blood transfusion are usually required. Typical findings of ACS on chest X ray (CXR) are segmental, lobar, or multifocal consolidation involving the lower lobes, with or without pleural effusion. Arterial blood gas (ABG) on room air should be performed in patients with SpO2 is less than 94%. Consideration should be given depending on the clinical scenario to perform blood culture, sputum culture, and nasopharyngeal swabs for viral etiologies.

Supplemental oxygen should be applied to patients with dyspnea, respiratory distress to maintain SpO2 >92% (or at patient’s baseline SpO2) and improved work of breathing. The proper use of incentive spirometry at least 10 inspirations every 2 hours has also shown benefit and prevent pulmonary complications4. Maintenance intravenous fluids should be given for the first 24-48 hours and later oral fluid intake should be encouraged. Fluid balance should be closely monitored to avoid fluid overload. Parental opioids are usually given via patient-controlled-analgesia (PCA) pump to prevent atelectasis. Empiric antibiotics covering atypical bacteria should be started immediately and include coverage of atypical bacteria due to high risk of infection. Simple blood transfusion is recommended when hemoglobin (Hb) drops 10-20% below baseline, decreasing hemoglobin trend, worsening symptoms, or radiographic signs without impending respiratory failure or as an interim measure for awaiting exchange transfusion. Exchange transfusion is indicated in previous history of severe ACS or cardiopulmonary disease, severe ACS without improvement with simple transfusion, presence of multilobar disease (>1 lobe affected) on CXR, severe hypoxemia (SaO2  85 or PaO2 55 mm Hg) and decreasing oxygen saturation despite increasing oxygen therapy. The goal of exchange transfusion is to improve Hb >10 g/dl or reduce HbS <30% of total Hb concentration2.

Hydroxyurea has been shown to reduce SCD complications, and increase HbF, total Hb levels, and life expectancy5. It is contraindicated in pregnancy and should be discontinued 3 months before conception6. For individuals who have two or more ACS episodes within 2 years despite maximal hydroxyurea therapy, chronic exchange transfusion can be considered. L-glutamine oral therapy showed reduced incidence of ACS with or without hydroxyurea, in patients the age of five years and older and was approved by FDA in 20177. Hemopoietic stem cell transplantation is indicated in patients who experience SCD complications despite hydroxyurea or chronic exchange transfusion8.

Catastrophic Antiphospholipid Antibody Syndrome

Antiphospholipid antibody syndrome (APS) is a multisystem autoimmune disease characterized by arterial or venous thromboembolism and/or pregnancy morbidity with persistently positive antiphospholipid antibody (aPL). Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare but life-threatening variant of APS characterized by rapid onset of symptoms, including multi-organ system failure secondary to macro and microvascular thrombosis. It is mostly found in females and affects <1% of all APS patients. It also associates with autoimmune diseases, mainly systemic lupus erythematosus (SLE)9. Almost two-third CAPS are caused by precipitating factors: infection (46.7%), malignancy (17.6%), surgery (16.8%), subtherapeutic anticoagulation (10.9%)10. The major organs involved in CAPS are renal (71%), brain (56%), lungs (55%), heart (53%), skin (45%), liver (34%).

1. Evidence of involvement of 3 or more organs, systems, and/or tissues
2. Development of manifestations simultaneously or in less than a week
3. Confirmation by histopathology of small vessel occlusion in at least 1 organ or tissue
4. Lab confirmation of presence of aPL
• Definite CAPS: Require all 4 Criteria
Probable CAPS
• All 4 criteria: except only 2 organs, systems and/or tissues involved.
• All 4 criteria: except for absence of lab confirmation of aPL
• Criteria 1,2 and 4
• Criteria 1,3 and 4, with the development of a third event more than a week but within 1 month of presentation despite anticoagulation

Table 1: Criteria of CAPS

The majority are found to have anticardiolipin IgG (83%) and IgM (38%), lupus anticoagulant (82%), and antinuclear antibodies (66%). Other findings include thrombocytopenia (46%), hemolytic anemia (35%), schistocytes (16%)11, increased acute phase protein and decreased complement levels.

A multidisciplinary approach is necessary to make a definitive diagnosis of CAPS, which includes hematology, intensive care team, nephrology, rheumatology, vascular surgeon and obstetric team and treatment always starts with identifying the underlying precipitating factors. Typical treatment may involve a combination of anticoagulation, glucocorticoids, and therapeutic plasma exchange (TPE) or intravenous immunoglobulin (IVIG)12.
The initial choice of anticoagulation is unfractionated heparin, subsequently transitioning to warfarin with a target INR of 2-3. Direct oral anticoagulants are contraindicated in CAPS due to the risk of thrombosis. If there is major bleeding, anticoagulation should be held and IV methylprednisolone or TPE and/or IVIG should be started. In cases with thrombocytopenia (platelet <50,000/microL), treatments with high dose dexamethasone, IVIG and/or thrombopoietin receptor agonists may be considered to increase platelet count which is essential for therapeutic anticoagulants initiation.
The McMaster guidelines recommended against steroid monotherapy; and recommended steroids in combination with heparin, IVIG, or plasmapheresis. A typical dose is intravenous methyl prednisone 0.5-1 G once daily for three days followed by oral prednisone 1 mg/kg with 4-6 weeks taper. There are no significant differences between TPE and IVIG, however, they should not be given simultaneously, and allow adequate time to transition from one to another13. Alternative treatment with rituximab (in microvascular thrombosis cases), or eculizumab (in complement-mediated thrombotic microangiopathy cases) should be considered in refractory cases, but sometimes can be used as initial therapy9. Low-dose aspirin can be given in addition to anticoagulation for those who cannot receive anticoagulation.

Hemophagocytic Lymphohistiocytosis (HLH)

HLH is a rare and life-threatening condition of excessive activation of immune system dysregulation, affecting multiorgan system failure. It has two types: familial (genetic) and acquired. Familial HLH is caused by a genetic mutation affecting the immune system, mostly found in children, and acquired HLH is caused by trigger factors such as infection, malignancy, or autoimmune disorders, which can be seen in both children and adults12. The clinical features are similar in both HLH types and can be present with nonspecific symptoms like fever, malaise, organomegaly (liver, spleen), lymphadenopathy, neurological symptoms, and other organ systems. As HLH carries a high mortality, early recognition, and prompt treatment of HLH is essential. To diagnosis HLH, 5 out of 8 of the following criteria must be fulfilled which can be clinical and require laboratory testing:

Initial workup with obtaining a detailed history is important in HLH as it is associated with genetic, and autoimmune disorders. Basic lab tests and imaging studies to identify the underlying triggers. Additional blood culture, lumbar puncture, viral panel if clinically indicated. Bone marrow evaluation should be performed to evaluate for cytopenia or hemophagocytosis, however, which is not pathognomonic for HLH. Special testing such as immunological profile, genetic and human leukocyte antigen (HLA) testing should be performed.

Management includes supportive treatment with pRBCs, platelets, fresh frozen plasma, cryoprecipitate, and TXA to reverse coagulopathy on Thromboelastography or other more traditional coagulation laboratory studies. Consider broad-spectrum antibiotics treatment of infection and aggressive blood pressure control as HLH patients are at high risk for posterior reversible encephalopathy syndrome (PRES). In clinically stable patients, the underlying triggers should be treated along with corticosteroids and monitored. In clinically unstable or deteriorating patients, HLH-specific treatment with 8 weeks of therapy with etoposide and dexamethasone with intrathecal therapy (hydrocortisone and methotrexate) can be started immediately in CNS involvement cases. Cyclosporine (Can utilize Tacrolimus as well which is slightly less nephrotoxic than cyclosporine) can be considered in severely ill patients. Allogenic Hematopoietic stem cell transplant (HSCT) is indicated in refractory or relapse or primary HLH cases or as a long-term curative therapy15.

Guest Post By:

Shoon Oo, MD
Internal Medicine Resident
Cape Fear Valley Health System
Fayetteville NC

Expert Peer Review:

Kenneth Snell MD
Surgical & Medical Oncology ICU
Department of Anesthesiology
H. Lee Moffitt Cancer Center and Research Institute
Assistant Professor
Morsani College of Medicine
University of South Florida, Tampa

David Goldenberg MD
Surgical & Medical Oncology ICU
Department of Anesthesiology
H. Lee Moffitt Cancer Center and Research Institute
Assistant Professor
Morsani College of Medicine
University of South Florida, Tampa


1. van Agtmael MA, Cheng JD, Nossent HC. Acute chest syndrome in adult Afro-Caribbean patients with sickle cell disease. Analysis of 81 episodes among 53 patients. Arch Intern Med. 1994 Mar 14;154(5):557-61. doi: 10.1001/archinte.154.5.557. PMID: 8122949.
2. Friend A, Settelmeyer TP, Girzadas D. Acute Chest Syndrome. 2023 Nov 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 28722902.
3. Ballas SK, Lieff S, Benjamin LJ, Dampier CD, Heeney MM, Hoppe C, Johnson CS, Rogers ZR, Smith-Whitley K, Wang WC, Telen MJ; Investigators, Comprehensive Sickle Cell Centers. Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol. 2010 Jan;85(1):6-13. doi: 10.1002/ajh.21550. PMID: 19902523; PMCID: PMC5046828.
4. Bellet PS, Kalinyak KA, Shukla R, Gelfand MJ, Rucknagel DL. Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med. 1995 Sep 14;333(11):699-703. doi: 10.1056/NEJM199509143331104. PMID: 7637747.
5. Agrawal RK, Patel RK, Shah V, Nainiwal L, Trivedi B. Hydroxyurea in sickle cell disease: drug review. Indian J Hematol Blood Transfus. 2014 Jun;30(2):91-6. doi: 10.1007/s12288-013-0261-4. Epub 2013 May 24. PMID: 24839362; PMCID: PMC4022916.
6. Jain D, Atmapoojya P, Colah R, Lodha P. Sickle Cell Disease and Pregnancy. Mediterr J Hematol Infect Dis. 2019 Jul 1;11(1):e2019040. doi: 10.4084/MJHID.2019.040. PMID: 31308916; PMCID: PMC6613624.
7. Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med. 2018 Jul 19;379(3):226-235. doi: 10.1056/NEJMoa1715971. PMID: 30021096.
8. Walters MC. Update of hematopoietic cell transplantation for sickle cell disease. Curr Opin Hematol. 2015 May;22(3):227-33. doi: 10.1097/MOH.0000000000000136. PMID: 25767957; PMCID: PMC5037959.
9. Rodríguez-Pintó I, Moitinho M, Santacreu I, Shoenfeld Y, Erkan D, Espinosa G, Cervera R; CAPS Registry Project Group (European Forum on Antiphospholipid Antibodies). Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev. 2016 Dec;15(12):1120-1124. doi: 10.1016/j.autrev.2016.09.010. Epub 2016 Sep 15. PMID: 27639837.
10. Kazzaz NM, McCune WJ, Knight JS. Treatment of catastrophic antiphospholipid syndrome. Curr Opin Rheumatol. 2016 May;28(3):218-27. doi: 10.1097/BOR.0000000000000269. PMID: 26927441; PMCID: PMC4958413.
11. Nayer A, Ortega LM. Catastrophic antiphospholipid syndrome: a clinical review. J Nephropathol. 2014 Jan;3(1):9-17. doi: 10.12860/jnp.2014.03. Epub 2014 Jan 1. PMID: 24644537; PMCID: PMC3956908.
12. Cervera R, Rodríguez-Pintó I, Legault K, Erkan D. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. Lupus. 2020 Oct;29(12):1594-1600. doi: 10.1177/0961203320951260. Epub 2020 Aug 20. PMID: 32819183.
13. Legault K, Schunemann H, Hillis C, Yeung C, Akl EA, Carrier M, Cervera R, Crowther M, Dentali F, Erkan D, Espinosa G, Khamashta M, Meerpohl JJ, Moffat K, O’Brien S, Pengo V, Rand JH, Rodriguez Pinto I, Thom L, Iorio A. McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome. J Thromb Haemost. 2018 Aug;16(8):1656-1664. doi: 10.1111/jth.14192. Epub 2018 Jul 5. PMID: 29978552.
14. Kim YR, Kim DY. Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults. Blood Res. 2021 Apr 30;56(S1):S17-S25. doi: 10.5045/br.2021.2020323. PMID: 33935031; PMCID: PMC8094004.
15. La Rosée P, Horne A, Hines M, von Bahr Greenwood T, Machowicz R, Berliner N, Birndt S, Gil-Herrera J, Girschikofsky M, Jordan MB, Kumar A, van Laar JAM, Lachmann G, Nichols KE, Ramanan AV, Wang Y, Wang Z, Janka G, Henter JI. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019 Jun 6;133(23):2465-2477. doi: 10.1182/blood.2018894618. Epub 2019 Apr 16. PMID: 30992265.

Post Peer Reviewed By: Frank Lodeserto, MD

Cite this article as: Shoon Oo, MD, "Hematologic Emergencies in the Critical Care Setting Part 2", REBEL EM blog, April 11, 2024. Available at: https://rebelem.com/hematologic-emergencies-in-the-critical-care-setting-part-2/.

Like this article?

Share on Facebook
Share on Twitter
Share on Linkdin
Share via Email

Want to support rebelem?