Advertisement

Pathological Features of Maternal Death From HELLP Syndrome

Chapter
Part of the Forensic Pathology Reviews book series (FPR, volume 1)

Summary

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is a life-threatening complication of preeclampsia during pregnancy or postpartum. Serious complications occur in 12.5-65% of cases of HELLP syndrome and are associated with a maternal mortality between 1.1 and 3.4%. Despite active research for many years, the etiology of this disorder exclusive to human pregnancy has not been sufficiently clarified. In clinical practice, disseminated intravascular coagulation (DIC) is found in 4-38% of cases with HELLP syndrome. Despite the apparent correlation between the marked degree of DIC in laboratory tests and the extent of laboratory changes in HELLP syndrome and the rate of maternal complications, the manifestation of DIC is neither an initial nor a principal symptom of HELLP syndrome but rather reflects a secondary pathophysiological process of the primary disease state that can be regarded as a result of preeclampsia that was diagnosed and/or treated too late. Hepatic rupture as a sequel of subcapsular liver hematoma in the course of DIC, occurring in 1-1.8% of cases, is considered the most serious and life-threatening maternal complication in HELLP syndrome. Hepatic rupture is located predominantly in the anterior-superior region of the right hepatic lobe and can occur both antepartum and postpartum. The main autopsy findings in HELLP syndrome are petechiae and suffusions in conjunctivae, skin and on mucous and serous surfaces of internal organs, cerebral edema, signs of acute respiratory distress syndrome (ARDS), edema of the lower extremities, hyperemia of the spleen, hydropericardium, and shock kidneys. Since these findings may be initiated by a variety of underlying pathologic conditions, they are highly unspecific. In contrast, liver pathology is a hallmark in the postmortem diagnosis of HELLP syndrome. At autopsy, the liver shows a rigid consistence with yellow-brown cut surfaces and confluent hemorrhagic foci on cross-sections of the liver parenchyma and occasionally subcapsular liver hematoma or hepatic rupture. The histopathological features of hepatic alterations in HELLP syndrome are periportal hepatocellular necrosis, hemorrhages sharply demarcated by an extended fibrin network from the surrounding unaffected liver parenchyma, and leukostasis in the liver sinusoids. In the kidneys, the glomeruli are primarily affected. They are enlarged and appear bloodless as a result of obliteration of the capillary lumina by swollen, vacuolated, and occasionally foamy endocapillary cells. In most cases, two characteristic capillary loop patterns of the glomeruli can be distinguished: (a) the cigar-shaped loop type presenting elongated, stretched, and obstructed loops, and (b) the pouting loop type showing enlarged glomerular tufts filling Bowman’s space with herniation of capillary loops into the proximal tubules. Relevant to medicolegal implications of a fatal outcome of HELLP syndrome is the point that the presenting symptoms of patients are generally highly unspecific. As a result, many of the patients are initially misdiagnosed with other medical or surgical disorders such as gastroenteritis, hepatitis, pyelonephritis, appendicitis, acute fatty liver of pregnancy, (AFLP), idiopathic thrombocytic purpura, and hemolytic uremic syndrome (HUS). Delay in diagnosis or expectant management of HELLP syndrome is implicated in a considerable number of cases with fatal outcome.

Key Words

HELLP syndrome pregnancy maternal death preeclampsia eclampsia disseminated intravascular coagulation (DIC) acute respiratory distress syndrome (ARDS) acute fatty liver of pregnancy (AFLP) thrombocytopenia renal pathology 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Pritchard JA, Weisman R, Ratnoff OD, Vosburgh GJ (1954) Intravascular hemolysis, thrombocytopenia and other hematologic abnormalities associated with severe toxemia of pregnancy. N Engl J Med 250, 89–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Weinstein L (1982) Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 142, 159–167.PubMedGoogle Scholar
  3. 3.
    Sibai BM, Taslimi MM, el-Nazer A, Amon E, Mabie BC, Ryan GM (1986) Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. Am J Obstet Gynecol 155, 501–509.PubMedGoogle Scholar
  4. 4.
    Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA (1993) Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) Am J Obstet Gynecol 169, 1000–1006.PubMedGoogle Scholar
  5. 5.
    Geary M (1997) The HELLP syndrome. Br J Obstet Gynaecol 104, 887–891.PubMedCrossRefGoogle Scholar
  6. 6.
    Rath W, Faridi A, Dudenhausen JW (2000) HELLP syndrome. J Perinat Med 28, 249–260.CrossRefGoogle Scholar
  7. 7.
    Onrust S, Santema JG, Aarnoudse JG (1999) Pre-eclampsia and the HELLP syndrome still cause maternal mortality in The Netherlands and other developed countries; can we reduce it? Eur J Obstet Gynecol Reprod Biol 82, 41–46.PubMedCrossRefGoogle Scholar
  8. 8.
    van Pampus MG, Wolf H, Westenberg SM, van der Post JA, Bonsel GJ, Treffers PE (1998) Maternal and perinatal outcome after expectant management of the HELLP syndrome compared with pre-eclampsia without HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 76, 31–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Visser W, Wallenburg HC (1995) Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe pre-eclampsia remote from term. Eur J Obstet Gynecol Reprod Biol 63, 147–154.PubMedCrossRefGoogle Scholar
  10. 10.
    Abbade JF, Peraoli JC, Costa RA, Calderon Id Ide M, Borges VT, Rudge MV (2002) Partial HELLP Syndrome: maternal and perinatal outcome. Sao Paulo Med J 120, 180–184.PubMedCrossRefGoogle Scholar
  11. 11.
    Sibai BM (1990) The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol 162, 311–316.PubMedGoogle Scholar
  12. 12.
    Audibert F, Friedman SA, Frangieh AY, Sibai BM (1996) Clinical utility of strict diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 175, 460–464.PubMedCrossRefGoogle Scholar
  13. 13.
    McCrae KR, Samuels P, Schreiber AD (1992) Pregnancy-associated thrombocytopenia: pathogenesis and management. Blood 80, 2697–2714.PubMedGoogle Scholar
  14. 14.
    Pridjian G, Puschett JB (2002) Preeclampsia. Part 1: clinical and pathophysiologic considerations. Obstet Gynecol Sury 57, 598–618.CrossRefGoogle Scholar
  15. 15.
    Fadigan AB, Sealy DP, Schneider EF (1994) Preeclampsia: progress and puzzle. Am Fam Physician 49, 849–856.PubMedGoogle Scholar
  16. 16.
    Jones SL (1998) HELLP! A cry for laboratory assistance: a comprehensive review of the HELLP syndrome highlighting the role of the laboratory. Hematopathol Mol Hematol 11, 147–171.PubMedGoogle Scholar
  17. 17.
    Benedetto C, Marozio L, Salton L, Maula V, Chieppa G, Massobrio M (2002) Factor V Leiden and factor II G20210A in preeclampsia and HELLP syndrome. Acta Obstet Gynecol Scand 81, 1095–1100.PubMedCrossRefGoogle Scholar
  18. 18.
    Welsch H, Krone HA (1994) Mütterliche Mortalität bei HELLP-Syndrom in Bayern 1983–1992. Zentralbl Gynakol 116, 202–206.PubMedGoogle Scholar
  19. 19.
    Isler CM, Rinehart BK, Terrone DA, Martin RW, Magann EF, Martin JN Jr. (1999) Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 181, 924–928.PubMedCrossRefGoogle Scholar
  20. 20.
    Soh Y, Yasuhi I, Nakayama D, Ishimaru T (2002) A case of postpartum cerebellar infarction with hemolysis, elevated liver enzymes, low platelets ( HELLP) syndrome. Gynecol Obstet Invest 53, 240–242.Google Scholar
  21. 21.
    Reubinoff BE, Schenker JG (1991) HELLP syndrome-a syndrome of hemolysis, elevated liver enzymes and low platelet count-complicating preeclampsiaeclampsia. Int J Gynaecol Obstet 36, 95–102.PubMedCrossRefGoogle Scholar
  22. 22.
    Van Dam PA, Renier M, Baekelandt M, Buytaert P, Uyttenbroeck F (1989) Disseminated intravascular coagulation and the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia. Obstet Gynecol 73, 97–102.PubMedGoogle Scholar
  23. 23.
    Hüskes KP, Baumgartner A, Hardt U, Klink F (1991) Doppelseitige, mehrzeitige Spontanruptur der Leber bei HELLP-Syndrom. Chirurg 62, 221–222.PubMedGoogle Scholar
  24. 24.
    Rath W, Loos W, Graeff H, Kuhn W (1992) Das HELLP-Syndrom. Gynäkologe 25, 430–440.PubMedGoogle Scholar
  25. 25.
    Reck T, Bussenius-Kammerer M, Ott R, Muller V, Beinder E, Hohenberger W (2001) Surgical treatment of HELLP syndrome-associated liver rupture-an update. Eur J Obstet Gynecol Reprod Biol 99, 57–65.PubMedCrossRefGoogle Scholar
  26. 26.
    Henny CP, Lim Cate JW AE, Brummelkamp WH, Buller HR, Ten Cate JW (1983) A review of the importance of acute multidisciplinary treatment following spontaneous rupture of the liver capsule during pregnancy. Surg Gynecol Obstet 156, 593–598.PubMedGoogle Scholar
  27. 27.
    Magann EF, Martin JN Jr. (1999) Twelve steps to optimal management of HELLP syndrome. Clin Obstet Gynecol 42, 532–550.PubMedCrossRefGoogle Scholar
  28. 28.
    Sheikh RA, Yasmeen S, Pauly MP, Riegler JL (1999) Spontaneous intrahepatic hemorrhage and hepatic rupture in the HELLP syndrome: four cases and a review. J Clin Gastroenterol 28, 323–328.PubMedCrossRefGoogle Scholar
  29. 29.
    Tsokos M, Longauer F, Kardosova V, Gavel A, Anders S, Schulz F (2002) Maternal death in pregnancy from HELLP syndrome. A report of three medicolegal autopsy cases with special reference to distinctive histopathological alterations. Int J Legal Med 116, 50–53.PubMedCrossRefGoogle Scholar
  30. 30.
    Schneider H (1994) Leberpathologie im Rahmen des HELLP-Syndroms. Arch Gynecol Obstet 255, Suppl 2: S245 - S254.Google Scholar
  31. 31.
    Sheehan HL (1980) Renal morphology in preeclampsia. Kidney Int 18, 241–252.PubMedCrossRefGoogle Scholar
  32. 32.
    Hill PA, Fairley KF, Kincaid-Smith P, Zimmerman M, Ryan GB (1988) Morphologic changes in the renal glomerulus and the juxtaglomerular apparatus in human preeclampsia. J Pathol 156, 291–303.PubMedCrossRefGoogle Scholar
  33. 33.
    Gaber LW, Spargo BH, Lindheimer MD (1994) The nephropathy of preeclampsiaeclampsia. In Tisher CC, Brenner BM, eds., Renal pathology with clinical and functional correlations. JB Lippincott Company, Philadelphia, pp. 419–441.Google Scholar
  34. 34.
    Gerth J, Busch M, Ott U, Grone HJ, Haufe CC, Funfstuck R, Sperschneider H, Stein G (2002) Schwangerschaftsassoziierte thrombotisehe Mikroangiopathie-eine diagnostische and therapeutische Herausforderung. Med Klin 97, 547–552.CrossRefGoogle Scholar
  35. 35.
    Symonds EM (1980) Aetiology of pre-eclampsia: a review. J R Soc Med 73, 871–875.PubMedGoogle Scholar
  36. 36.
    Hill PA, Fairley KF, Kincaid-Smith P, Zimmerman M, Ryan GB (1988) Morphologic changes in the renal glomerulus and the juxtaglomerular apparatus in human preeclampsia. J Pathol 156, 291–303.PubMedCrossRefGoogle Scholar
  37. 37.
    Rath W, Loos W, Kuhn W (1994) Das HELLP-Syndrom. Zentralbl Gynakol 116, 195–201.PubMedGoogle Scholar
  38. 38.
    Bauer TW, Moore GW, Hutchins GM (1982) Morphologic evidence for coronary artery spasm in eclampsia. Circulation 65, 255–259.PubMedCrossRefGoogle Scholar
  39. 39.
    Todd GL, Baroldi G, Pieper GM, Clayton FC, Eliot RS (1985) Experimental catecholamine-induced myocardial necrosis. I. Morphology, quantification and regional distribution of acute contraction band lesions. J Mol Cell Cardiol 17, 317–338.PubMedCrossRefGoogle Scholar
  40. 40.
    Armiger LC, Smeeton WM (1986) Contraction-band necrosis: patterns of distribution in the myocardium and their diagnostic usefulness in sudden cardiac death. Pathology 18, 289–295.PubMedCrossRefGoogle Scholar
  41. 41.
    Karch SB (1987) Resuscitation-induced myocardial necrosis. Catecholamines and defibrillation. Am J Forensic Med Pathol 8, 3–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Yoshida K, Ogura Y, Wakasugi C (1992) Myocardial lesions induced after trauma and treatment. Forensic Sci Int 54, 181–189.PubMedCrossRefGoogle Scholar
  43. 43.
    Baroldi G, Mittleman RE, Parolini M, Silver MD, Fineschi V (2001) Myocardial contraction bands. Definition, quantification and significance in forensic pathology. Int J Legal Med 115, 142–151.PubMedCrossRefGoogle Scholar
  44. 44.
    Baroldi G, Silver MD, De Maria R, Parolini M, Turillazzi E, Fineschi V (2003) Frequency and extent of contraction band necrosis in orthotopically transplanted human hearts. A morphometric study. Int J Cardiol 88, 267–278.PubMedCrossRefGoogle Scholar
  45. 45.
    Ades, CJ, Strutton GM, Walker, NI, Furnival CM, Whiting, G (1989) Spontaneous rupture of the liver associated with amyloidosis. J Clin Gastroenterol 11, 85–87.PubMedCrossRefGoogle Scholar
  46. 46.
    Cozzi, PJ, Morris, DL (1996) Two cases of spontaneous liver rupture and literature review. HPB Surg 9, 257–260.PubMedCrossRefGoogle Scholar
  47. 47.
    Flowers, BF, McBurney, RP, Vera, SR (1990) Ruptured hepatic adenoma. A spectrum of presentation and treatment. Am Surg 56, 380–383.Google Scholar
  48. 48.
    Kühböck, J, Radaszkiewicz, T, Walek, H (1975) Peliosis hepatic, complicating treatment with anabolic steroids. Med Klin 70, 1602–1607.PubMedGoogle Scholar
  49. 49.
    Balasegaram M (1968) Spontaneous intraperitoneal rupture of primary liver-cell carcinoma. Aust NZJ Surg 37, 332–337.CrossRefGoogle Scholar
  50. 50.
    Mokka R, Seppäla A, Huttunen R, Kairaluoma M, Sutinen S, Larmi TKI (1976) Spontaneous rupture of liver tumours. Br J Surg 63, 715–717.PubMedCrossRefGoogle Scholar
  51. 51.
    Ooi LL, Lynch SV, Graham DA, Strong RW (1996) Spontaneous liver rupture in amyloidosis. Surgery 120, 117–119.PubMedCrossRefGoogle Scholar
  52. 52.
    Ong GB, Taw JL (1972) Spontaneous rupture of hepatocellular carcinoma. Br Med J 4, 146–149.PubMedCrossRefGoogle Scholar
  53. 53.
    Mabie WC (1991) Acute fatty liver of pregnancy. Crit Care Clin 7, 799–808.PubMedGoogle Scholar
  54. 54.
    Bacq Y (1998) Acute fatty liver of pregnancy. Semin Perinatol 22, 134–140.PubMedCrossRefGoogle Scholar
  55. 55.
    Chang JC, Kathula SK (2002) Various clinical manifestations in patients with thrombotic microangiopathy. J Investig Med 50, 201–206.PubMedCrossRefGoogle Scholar
  56. 56.
    McCrae KR, Cines DB (1997) Thrombotic microangiopathy during pregnancy. Sem Hematol 34, 148–158.Google Scholar
  57. 57.
    Faridi A, Heyl W, Rath W (2000) Preliminary results of the International HELLPMulticenter-Study. Int J Gynecol Obstet 69, 279–280.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

There are no affiliations available

Personalised recommendations