eMedicine Specialties > Emergency Medicine > Infectious Diseases

Hantavirus Cardiopulmonary Syndrome: Differential Diagnoses & Workup

Author: Juliet D Caldwell, MD, Assistant Professor, Department of Emergency Medicine, Weill Medical College of Cornell University; Attending Physician, Department of Emergency Medicine, New York Presbyterian Hospital, Weill-Cornell Medical Center
Contributor Information and Disclosures

Updated: Jan 29, 2009

Differential Diagnoses

Acute Respiratory Distress Syndrome
Pneumonia, Mycoplasma
CBRNE - Anthrax Infection
Pneumonia, Viral
CBRNE - Plague
Pneumonic plague
CBRNE - Q Fever
Salicylate toxicity with pulmonary edema
Dengue Fever
Shock, Cardiogenic
HIV Infection and AIDS
Shock, Septic
Leptospirosis in Humans
Toxicity, Phosgene Influenza
Phosphine toxicity
Tularemia
Pneumonia, Bacterial
Pneumonia, Immunocompromised

Workup

Laboratory Studies

Laboratory results vary with the phase of disease.

  • Complete blood cell count (CBC): The CBC is the most useful test to obtain. It should be checked on arrival as well as 24 hours after presentation.
    • Platelets: Platelets may initially be normal but ultimately at least a moderate decline in count will be demonstrated, sometimes as early as the prodromal phase.23 In patients with Hantavirus cardiopulmonary syndrome (HCPS), 98% present with a platelet count <150 X 109/L and all patients eventually develop a platelet count <100 X 109/L. A dramatic fall sometimes heralds the cardiopulmonary phase of HCPS.
    • White blood cell (WBC) count with peripheral blood smear: Leukocytosis and occasionally leukopenia are the norm. More importantly, severe clinical course can reliably be predicted by the appearance of a marked leukocytosis (as high as 90,000 cells/microL) and the appearance of immunoblasts (circulating atypical lymphocytes) (see Media file 7).27 Thrombocytopenia, a left shift on peripheral smear, and an immunoblast count that exceeds 10% of the total lymphoid series has been termed the diagnostic triad of HCPS.28 In experienced centers that see relatively high numbers of HCPS, this triad alerts practitioners to begin preparation for transfer to a center capable of aggressive critical care management and possibly ECMO.
Hantavirus cardiopulmonary syndrome (HCPS) immuno...

Hantavirus cardiopulmonary syndrome (HCPS) immunoblast.

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Hantavirus cardiopulmonary syndrome (HCPS) immuno...

Hantavirus cardiopulmonary syndrome (HCPS) immunoblast.


    • Hematocrit (HCT): Hemoconcentration is due to massive capillary leak and portends a poor prognosis. Hematocrits >50% in men and >48% in women may occur during the cardiopulmonary phase of HCPS and is a marker of severe disease.29 This occurs in only 50% of cases.
    • In the prodromal phase, the CBC may be normal or show slight thrombocytopenia only.  
  • Chemistries
    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels are often elevated, sometimes as early as the prodromal phase of HCPS. Levels can elevate 2-5 times their reference values.
    • Creatinine level: SNV rarely causes renal failure; however, the Black Creek Canal, Bayou, and Andes viruses have higher rates of renal insufficiency.
    • Creatine phosphokinase (CPK) level: SNV rarely causes CPK elevations (again unlike the Bayou, Black Creek Canal, and Andes viruses).
  • Coagulation studies
    • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are usually within the reference range in SNV infection. However, a few cases of disseminated intravascular coagulation (DIC) have been associated with HCPS.
  • Arterial blood gases (ABGs) measurement: Progressive metabolic acidosis and severe hypoxemia mark the cardiopulmonary phase of HCPS.
  • Lactate level: Levels as high as 9.5 mg/dL have been recorded in severe HCPS. A lactate level greater than 4 has been associated with high mortality rates.
  • Serologic assays: Definitive diagnosis of HCPS is made on the basis of 1 of 3 assays.
    • Enzyme-linked immunosorbent assay detects circulating immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to SNV. All patients have IgM and most have IgG by the time symptoms are evident.
    • Western blot and strip blot assays are the most commonly used. They use a nucleocapsid (N) antigen for the detection of Hantavirus antibodies. The rapid immunoblot strip assay (RIBA), developed by UNM, is a dipstick-type test that detects SNV antibodies in the clinical phase of the disease with 100% sensitivity.
    • Acute infection can be distinguished from past exposure by the presence of IgM antibodies or by a 4-fold increase in serum IgG antibodies.
    • Postmortem assays can be accomplished by using immunohistochemical tests for N-antigens. Viral RNA can also be detected using reverse-transcription-polymerase chain reaction (PCR).

Imaging Studies

  • Radiography
    • At presentation, approximately one third of patients show evidence of pulmonary edema on chest radiograph. Within 48 hours, virtually all patients demonstrate pulmonary edema and two thirds have progressed to severe bilateral airspace disease. Although chest radiographic findings on presentation are often normal, onset of the cardiopulmonary phase brings about a characteristic radiologic evolution (see Media file 8).30 Mild interstitial pulmonary edema progresses to severe bilateral alveolar edema in a basilar or perihilar pattern.
Chest radiographic progression of Hantavirus card...

Chest radiographic progression of Hantavirus cardiopulmonary syndrome (HCPS).

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Chest radiographic progression of Hantavirus card...

Chest radiographic progression of Hantavirus cardiopulmonary syndrome (HCPS).


    • Pleural effusions are common.
    • Heart size is normal (barring concomitant heart disease).
  • Echocardiography
    • Occasionally, echocardiography is useful to distinguish cardiogenic pulmonary edema from the noncardiogenic edema typically seen in HCPS.
    • Global cardiac dysfunction may occur in the later stages of HCPS.

Procedures

  • A flow-directed pulmonary artery catheterization (PAC), or Swan-Ganz catheter, is frequently a useful tool to aid in resuscitative fluid management of HCPS. As HCPS demonstrates a characteristic hemodynamic profile, it can also offer valuable diagnostic and prognostic information. A low pulmonary artery occlusion pressure (consistent with a pulmonary capillary leak) and a low cardiac index characterize early HCPS.
    • Advanced HCPS yields a severe drop in cardiac index and an increased systemic vascular resistance index (SVRI).
    • A cardiac index of less than 2 L/min/m2 (one marker used to predict a 100% mortality without further intervention) has been used successfully as criteria to initiate rescue ECMO therapy.31

More on Hantavirus Cardiopulmonary Syndrome

Overview: Hantavirus Cardiopulmonary Syndrome
Differential Diagnoses & Workup: Hantavirus Cardiopulmonary Syndrome
Treatment & Medication: Hantavirus Cardiopulmonary Syndrome
Follow-up: Hantavirus Cardiopulmonary Syndrome
Multimedia: Hantavirus Cardiopulmonary Syndrome
References
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References

  1. Sheedy JA, Froeb HF, Batson HA, et al. The clinical course of epidemic hemorrhagic fever. Am J Med. May 1954;16(5):619-28. [Medline].

  2. Lee HW, Baek LJ, Johnson KM. Isolation of Hantaan virus, the etiologic agent of Korean hemorrhagic fever, from wild urban rats. J Infect Dis. Nov 1982;146(5):638-44. [Medline].

  3. Brummer-Korvenkontio M, Vaheri A, Hovi T, et al. Nephropathia epidemica: detection of antigen in bank voles and serologic diagnosis of human infection. J Infect Dis. Feb 1980;141(2):131-4. [Medline].

  4. Avsic-Zupanc T, Xiao SY, Stojanovic R, Gligic A, van der Groen G, LeDuc JW. Characterization of Dobrava virus: a Hantavirus from Slovenia, Yugoslavia. J Med Virol. Oct 1992;38(2):132-7. [Medline].

  5. Tsai TF, Bauer SP, Sasso DR, et al. Serological and virological evidence of a Hantaan virus-related enzootic in the United States. J Infect Dis. Jul 1985;152(1):126-36. [Medline].

  6. Glass GE, Watson AJ, LeDuc JW, Childs JE. Domestic cases of hemorrhagic fever with renal syndrome in the United States. Nephron. 1994;68(1):48-51. [Medline].

  7. Centers for Disease Control and Prevention. From the Centers for Disease Control and Prevention. Infectious diseases update: outbreak, hantavirus infection--southwestern United States, 1993. JAMA. Jul 7 1993;270(1):25. [Medline].

  8. Centers for Disease Control and Prevention. All About Hantavirus Web site. Available at http://www.cdc.gov/ncidod/diseases/hanta/hps.

  9. Klein SL, Calisher CH. Emergence and persistence of hantaviruses. Curr Top Microbiol Immunol. 2007;315:217-52. [Medline].

  10. Hjelle B, Glass GE. Outbreak of hantavirus infection in the Four Corners region of the United States in the wake of the 1997-1998 El Nino-southern oscillation. J Infect Dis. May 2000;181(5):1569-73. [Medline].

  11. Trencseni T, Keleti B. Clinical aspects and epidemiology of haemorrhagic fever with renal syndrome. Budapest. Akademai Kiado. 1971.

  12. Lazaro ME, Cantoni GE, Calanni LM, et al. Clusters of hantavirus infection, southern Argentina. Emerg Infect Dis. Jan 2007;13(1):104-10. [Medline].

  13. Terajima M, Hendershot JD 3rd, Kariwa H, et al. High levels of viremia in patients with the Hantavirus pulmonary syndrome. J Infect Dis. Dec 1999;180(6):2030-4. [Medline].

  14. Xiao R, Yang S, Koster F, Ye C, Stidley C, Hjelle B. Sin Nombre viral RNA load in patients with hantavirus cardiopulmonary syndrome. J Infect Dis. Nov 15 2006;194(10):1403-9. [Medline].

  15. Mertz GJ, Hjelle BL, Bryan RT. Hantavirus infection. Adv Intern Med. 1997;42:369-421. [Medline].

  16. Maes P, Clement J, Gavrilovskaya I, Van Ranst M. Hantaviruses: immunology, treatment, and prevention. Viral Immunol. 2004;17(4):481-97. [Medline].

  17. Peters CJ, Simpson GL, Levy H. Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Annu Rev Med. 1999;50:531-45. [Medline].

  18. Nolte KB, Feddersen RM, Foucar K, et al. Hantavirus pulmonary syndrome in the United States: a pathological description of a disease caused by a new agent. Hum Pathol. Jan 1995;26(1):110-20. [Medline].

  19. Hallin GW, Simpson SQ, Crowell RE, et al. Cardiopulmonary manifestations of hantavirus pulmonary syndrome. Crit Care Med. Feb 1996;24(2):252-8. [Medline].

  20. Entwisle G, Hale E. Hemodynamic alterations in hemorrhagic fever. Circulation. Mar 1957;15(3):414-25. [Medline].

  21. Padula PJ, Edelstein A, Miguel SD, Lopez NM, Rossi CM, Rabinovich RD. [Epidemic outbreak of Hantavirus pulmonary syndrome in Argentina. Molecular evidence of person to person transmission of Andes virus]. Medicina (B Aires). 1998;58 Suppl 1:27-36. [Medline].

  22. Young JC, Hansen GR, Graves TK, et al. The incubation period of hantavirus pulmonary syndrome. Am J Trop Med Hyg. Jun 2000;62(6):714-7. [Medline].

  23. Johnson AM, Bowen MD, Ksiazek TG, et al. Laguna Negra virus associated with HPS in western Paraguay and Bolivia. Virology. Nov 10 1997;238(1):115-27. [Medline].

  24. Chang B, Crowley M, Campen M, Koster F. Hantavirus cardiopulmonary syndrome. Semin Respir Crit Care Med. Apr 2007;28(2):193-200. [Medline].

  25. Castillo C, Naranjo J, Sepulveda A, Ossa G, Levy H. Hantavirus pulmonary syndrome due to Andes virus in Temuco, Chile: clinical experience with 16 adults. Chest. Aug 2001;120(2):548-54. [Medline].

  26. Fulhorst CF, Milazzo ML, Armstrong LR, et al. Hantavirus and arenavirus antibodies in persons with occupational rodent exposure. Emerg Infect Dis. Apr 2007;13(4):532-8. [Medline].

  27. Jenison S, Hjelle B, Simpson S, Hallin G, Feddersen R, Koster F. Hantavirus pulmonary syndrome: clinical, diagnostic, and virologic aspects. Semin Respir Infect. Dec 1995;10(4):259-269. [Medline].

  28. Hjelle B. Hantavirus Cardiopulmonary Syndrome. UpToDate. 2008.

  29. Duchin JS, Koster FT, Peters CJ, et al. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group. N Engl J Med. Apr 7 1994;330(14):949-55. [Medline].

  30. Ketai LH, Williamson MR, Telepak RJ, et al. Hantavirus pulmonary syndrome: radiographic findings in 16 patients. Radiology. Jun 1994;191(3):665-8. [Medline].

  31. Dietl CA, Wernly JA, Pett SB, et al. Extracorporeal membrane oxygenation support improves survival of patients with severe Hantavirus cardiopulmonary syndrome. J Thorac Cardiovasc Surg. Mar 2008;135(3):579-84. [Medline].

  32. Dull SM, Brillman JC, Simpson SQ, Sklar DP. Hantavirus pulmonary syndrome: recognition and emergency department management. Ann Emerg Med. Sep 1994;24(3):530-6. [Medline].

  33. Levy H, Simpson SQ. Hantavirus pulmonary syndrome. Am J Respir Crit Care Med. Jun 1994;149(6):1710-3. [Medline].

  34. Crowley MR, Katz RW, Kessler R, et al. Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation. Crit Care Med. Feb 1998;26(2):409-14. [Medline].

  35. Huggins JW, Hsiang CM, Cosgriff TM, et al. Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome. J Infect Dis. Dec 1991;164(6):1119-27. [Medline].

  36. Chapman LE, Mertz GJ, Peters CJ, et al. Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group. Antivir Ther. 1999;4(4):211-9. [Medline].

  37. Mertz GJ, Miedzinski L, Goade D, et al. Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America. Clin Infect Dis. Nov 1 2004;39(9):1307-13. [Medline].

  38. Bharadwaj M, Nofchissey R, Goade D, Koster F, Hjelle B. Humoral immune responses in the hantavirus cardiopulmonary syndrome. J Infect Dis. Jul 2000;182(1):43-8. [Medline].

  39. Jonsson CB, Hooper J, Mertz G. Treatment of hantavirus pulmonary syndrome. Antiviral Res. Apr 2008;78(1):162-9. [Medline].

  40. Custer DM, Thompson E, Schmaljohn CS, Ksiazek TG, Hooper JW. Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine. J Virol. Sep 2003;77(18):9894-905. [Medline].

  41. Hooper JW, Custer DM, Smith J, Wahl-Jensen V. Hantaan/Andes virus DNA vaccine elicits a broadly cross-reactive neutralizing antibody response in nonhuman primates. Virology. Mar 30 2006;347(1):208-16. [Medline].

  42. Schmaljohn CS, Chu YK, Schmaljohn AL, Dalrymple JM. Antigenic subunits of Hantaan virus expressed by baculovirus and vaccinia virus recombinants. J Virol. Jul 1990;64(7):3162-70. [Medline].

  43. Xu X, Ruo SL, McCormick JB, Fisher-Hoch SP. Immunity to Hantavirus challenge in Meriones unguiculatus induced by vaccinia-vectored viral proteins. Am J Trop Med Hyg. Oct 1992;47(4):397-404. [Medline].

  44. Howard MJ, Doyle TJ, Koster FT, et al. Hantavirus pulmonary syndrome in pregnancy. Clin Infect Dis. Dec 1999;29(6):1538-44. [Medline].

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Further Reading

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Keywords

hantavirus, hantavirus pulmonary syndrome, HCPS, hanta, Sin Nombre virus, deer mouse, Peromyscus maniculatus, Muerto Canyon virus, four corners virus, Hantaan virus, hemorrhagic fever with renal syndrome, HFRS, HPS

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Contributor Information and Disclosures

Author

Juliet D Caldwell, MD, Assistant Professor, Department of Emergency Medicine, Weill Medical College of Cornell University; Attending Physician, Department of Emergency Medicine, New York Presbyterian Hospital, Weill-Cornell Medical Center
Juliet D Caldwell, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Michelle Ervin, MD, Chair, Department of Emergency Medicine, Howard University Hospital
Michelle Ervin, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, National Medical Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Barry J Sheridan, DO, Chief, Department of Emergency Medical Services, Brooke Army Medical Center
Barry J Sheridan, DO is a member of the following medical societies: American Academy of Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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