Low haptoglobin, reflex: hemolysis!
Dresselaars, H.F., Hem, K.G. van der
Voorzitter(s): mw. prof.dr. J. de Graaf, Nijmegen & mw. dr. E.J.M. Mattijssen, Arnhem
Locatie(s): Auditorium 2
Categorie(ën):
A 56 year-old female Creole patient was referred by her general practitioner because of a mild normocytic anemia. Her medical history consisted of recurrent urinary tract infections in the past. She did not use any medications.Anamnesis and physical examination were unremarkable. Laboratory results showed Hb 7.1 mmol/l, MCV 87 fl, leukocytes 4.2 x10E9/l with normal differentiation, platelets 315 x10E9/l, ESR 20 mm after 1 hour, reticulocytes 55.60 x10^9/l, creatinin 77 micromol/l, albumin 42 g/l, ASAT 23 U/l, ALAT 18 U/l, total bilirubin 6 umol/l, GGT 19 U/l, alkaline phosphatase 88 U/l, lactate dehydrogenase (LDH) 181 U/l, CRP 3.9 mg/l, iron 15.3 umol/l, total iron binding capacity 40.2 umol/l, transferrin saturation 38 %, ferritin 109 ug/l, haptoglobin
HIV serology was negative, cerulosplasmin levels were normal and no thalassemia could be found. There was no evidence of paroxysmal nocturnal hemoglobinuria, erythrocytic enzymes were present in normal levels and no splenic abnormalities were seen by echography. While haptoglobin remained undetectably low with normal LDH and bilirubin and Hb remained stable at 7.5 mmol/l, it was concluded there was no hemolysis. Subsequent determination of hemopexin showed a normal value of 1010 mg/l (500-1150 mg/l), indicating absence of severe or chronic hemolysis. The diagnosis congenital anhaptoglobinemia was made.
An- or hypohaptoglobinemia can both be acquired or congenital. The acquired condition is due to increased consumption in hemolysis or decreased synthesis in liver dysfunction. Congenitally allelic deletion in the Hp-gene cluster leads to decrease or absence of haptoglobin. Hemopexin levels can differentiate between the two forms: since hemopexin binds free heme its level decreases after saturation of the hemoglobin-binding capacity of haptoglobin. When haptoglobin is low in absence of hemolysis hemopexin levels are normal.
Different fenotypes of congenital haptoglobin deficiency exist. In true anhaptoglobinemia a silent allele with no gene product is inherited (Hp 0). Hp 0-0 phenotype is present in approximately 1 in 1000 Caucasians. In black people (especially from West Africa) anhaptoglobinemia is more frequent (>30%).
Diagnosing hypohaptoglobinemia has important clinical consequences since it is associated with heme accumulation resulting in iron-driven oxidative stress and vitamin C depletion. In addition, it predisposes for allergic transfusion reactions containing traces of haptoglobin when haptoglobin antibodies are present.