ISSN 0008-5286

THE CANADIAN VETERINARY LA REVUE VETERINAIRE

JOURNAL CANADIENNE
Volume 23 November-novembre No. 11

Bovine Postparturient Hemoglobinuria:

A Review of the Literature
P.S. MACWILLIAMS, G.P. SEARCY AND J.E.C. BELLAMY
Department of Veterinary Pathology, School of Veterinary Medicine,
Louisiana State University, Baton Rouge, Louisiana 70803 (MacWilliams)
and Department of Veterinary Pathology, Western College of Veterinary
Medicine, University of Saskatchewan, Saskatoon, Saskatchewan 57N 0 WO (Searcy and Bellamy)

SUMMARY parturient hemoglobinuria is a spo- number and diversity of etiological

Predisposing causes of bovine post- radic disease of multiparous, high factors associated with the disease.
parturient hemoglobinuria are sum- producing dairy cattle characterized Early investigators searched for bac-
marized along with suspected patho- by intravascular hemolysis, hemoglo- terial hemolysins or blood parasites
geneses, clinical signs, laboratory binuria and anemia. The incidence of such as Babesia spp. as etiological
findings, clinical management and the disease in the total cattle popula- agents (16). Animal transmission stud-
early experimentation. tion is very low with a case fatality rate ies using blood, urine and intestinal
ranging from 10 to 50% (2). Occasion- filtrates have been unsuccessful. Sub-
R ASU M t ally, farms with a particularly high sequent papers concluded that PPH
Une revue de la litterature relative a incidence may be encountered but was neither infectious nor contagious
l'hemoglobinurie puerperale bovine usually only one or two cases are clini- based on negative serological and bac-
Les auteurs presentent un resume des cally apparent at one time (6,7). In 39 teriological evidence for pathogenic
causes predisposantes, de la patho- cases of PPH, an interval of 11 to 42 bacteria and failure to identify ery-
genese probable, des signes cliniques, days was reported between parturition throcyte parasites (2,5,7,11,17,18).
des resultats d'epreuves de laboratoire, and the onset of clinical signs (2). Sim- A disease in Ontario known as "red
de l'approche clinique et des premieres ilarly, 19 of 27 cases documented in water" was associated with several
experiences concernant l'hemoglobi- Australia occurred within 30 days of predisposing factors which included:
nurie puerperale bovine. calving (8). The occurrence of this a) recent parturition, b) heavy milk
syndrome in bulls, antepartum cows, production, c) dietary phosphorus
H I S TO R Y heifers less than two years old, or beef deficiency and d) consumption of tur-
In the latter half of the nineteenth cen- cows is unusual but has been reported nips, rape, kale, green alfalfa and
tury, hemoglobinuria was report- (6,9). A disease with many similarities sugar beet pulp (3,9,19). In addition,
ed in Scottish cattle following parturi- has been described in sheep (10), Egyp- many cows were hypophosphatemic
tion (1). Similar descriptions from tian and Indian buffaloes (1 1,12) and a (2,20,21).
Africa, Asia, Australia, Europe and goat (13). Since the 1930's, the list of feeds
North America followed under a vari- The disease is usually seen in adult associated with PPH (Table I) has ex-
ety of different names. Parturient dairy cattle during their third to sixth panded to include: a) sugar beet roots
hemoglobinemia or hemoglobinuria lactation (5,14). Postparturient hemo- (mangels) and leaves, b) field crops
(2), red water (3) and nutritional hemo- globinuria tends to occur during the such as green oats, perennial ryegrass,
globinuria (4) have been used syn- winter months, especially when pre- Egyptian clover and alfalfa and
onymously with postparturient hemo- ceded by a dry growing season (15,16). c) members of the genus Brassica,
globinuria (PPH) which is the often referred to as cruciferous plants.
designation favored in many publica- ETIOLOGY AND PATHOGENESIS In addition to their low phosphorus
tions (5). The pathogenesis of erythrocyte de- content (< 0.4% dry matter) or high
struction leading to anemia and calcium to phosphorus ratio (> 2:1),
INCIDENCE AND OCCURRENCE hemoglobinuria in PPH is unknown. some feeds (e.g. rape and kale) in
As described in North America, post- In part, this is probably due to the Table I contain hemolytic substances
Present address of senior author: Hazleton Raltech, Inc., Madison, Wisconsin 53707.

Can. vet. J. 23: 309-312 (November 1982) 309

(31,32). Hemolytic saponins from PPH (36,37). The incidence of PPH The acute disease (three to five days)
sugar beets or alfalfa may interact with was significantly lower (5.18% versus can terminate in death or be followed
a low serum phosphorus concentra- 25.51%; P < 0.01) in cows treated with by prolonged convalescence (two to
tion to produce PPH (6). It has also copper prior to calving. Futhermore, a eight weeks). Ketonuria and a
been postulated that phosphorus defi- top dressing of copper sulfate to pas- depraved appetite may occur during
ciency was a "necessary predisposing tures four months prior to calving was recovery (14). Gangrene and sloughing
factor" and that feeding cruciferous followed by an increase in pasture, of the extremities (digits, tail, ears and
plants precipitated the hemolytic crisis blood and liver concentrations of teats) are reported sequelae. Recov-
(17). copper and a marked decrease in the ered animals regain their former body
Copper deficiency has been sug- incidence of PPH. In New Zealand, condition and milk production slowly.
gested as a possible etiology of PPH by hypophosphatemia was not a consis- The recommended treatment for
workers in New Zealand. Cattle from tent finding in PPH. PPH in North America includes: a) in-
dairy farms with a high incidence of travenous infusion of sodium acid-
PPH had low levels of copper in serum CLINICAL SIGNS, DIAGNOSIS phosphate (60 g in 300 mL of water),
and liver (33). A recent application of AND TREATMENT b) 100 g of bone meal administered as
lime or molybdate fertilizer to grazing Hemoglobinuria is often the premoni- a drench twice a day, c) transfusion of
land was a feature common to these tory clinical sign before anemia, fresh blood as indicated and d) intra-
farms. Analysis of pasture samples depression, inappetence, or decreased venous fluids to maintain hydration
revealed high concentrations of milk production are observed (2). As (2,14,38). Correction of any phos-
molybdenum and low levels of copper, the anemia develops, mucous mem- phorus deficiency or imbalance in the
especially during the months of high- branes become pale and may become ration along with removal of incrimi-
est disease incidence (July, August, icteric. As the heart rate increases (80- nated feeds (Table I) may prevent
September and October). Since 130 beats/ min), breathing becomes additional cases. Because of inconsis-
molybdenum may interfere with rapid and shallow. Affected cows are tent results with phosphate therapy
copper absorption from the gut, the weak and often recumbent. Forced and the copper-deficient status of
copper-deficient status of the cattle exercise at this time can be fatal. The affected cows, workers in New Zea-
may have been induced by the applica- feces may be firm, dry and bile- land suggest parenteral copper
tion of excessive molybdenum to pas- stained, or fetid and diarrheic. An ele- (120 mg available copper per cow) as
tures (34,35). Parenteral administra- vated body temperature (up to 40°C) the preferred treatment (34).
tion of copper has been effectual in in the early stages and intense thirst are
dairy herds with prior histories of variable features. LABORATORY FINDINGS
Hematologically, PPH has the fea-
TABLE I tures of an acute intravascular hemo-
CALCIUM AND PHOSPHORUS CONTENT OF FEEDS (22) lytic anemia. The packed cell volume
ASSOCIATED WITH PPH falls rapidly to its lowest level four to
Feed Caa Pa Reference(s)
nine days after the onset of hemoglo-
binuria (2). The plasma, initially
Alfalfa (Medicago sativa) 2,9,6 hemoglobinemic, becomes icteric as
aerial part, fresh 2.01 0.28
the destruction of erythrocytes pro-
Brussels Sprouts (Brassica oleracea germmifera) 23 gresses. Morphologically, the anemia
heads, fresh 0.27 0.54
is characterized by evidence of intensi-
Cabbage (Brassica oleracea capitata) 13,23 fied erythrogenesis. Polychromasia,
leaves, fresh 0.63 0.21
whole, fresh 0.66 0.39 anisocytosis, macrocytosis, basophilic
Clover, Egyptian (Trifolium alexandrium) 11,18,27,28
stippling, reticulocytosis and in-
aerial part, fresh 3.56 0.32 creased numbers of metarubricytes are
Kale (Brassica oleracea acephala) 1,9,10,23
commonly seen on stained blood
aerial part, fresh 1.61 0.51 films. Swollen erythrocytes with
Oats (Avena sativa) 17,30
dimpled centers and thorn-apple
aerial part, fresh 0.28 0.31 shaped erythrocytes were described in
Rape (Brassica spp.) 9,10,18
1940 (39) and may be comparable to
aerial part, fresh 1.47 0.43 echinocytes in the current nomencla-
Ryegrass, Perennial (Lolium perenne) 29
ture. Results for erythrocyte osmotic
aerial part, fresh 0.53 0.37 fragility have been conflicting. A
Sugar Beet (Beta saccharifera) 2,5,6,9,16,25,26 period of increased erythrocyte
pulp, dehydrated 0.75 0.10 osmotic fragility was reported imme-
aerial part, fresh 1.01 0.22 diately after parturition in a cow which
roots (mangels) 0.24 0.24 subsequently developed PPH (40).
Turnip (Brassica rapa) 9,24 Others have found normal erythrocyte
roots, fresh 0.56 0.28 osmotic fragility (8,19,35). A neutro-
aerial part, fresh 2.92 0.51 philic leukocytosis is often observed
Expressed as percent dry matter. during the hemolytic crisis.

310
 In addition to studies implicating a cies) produced clinical signs of PPH 19 gators. However, it is also possible that
copper-molybdenum imbalance, days after the third calving (40). Signs the syndrome in New Zealand repre-
Heinz bodies have been found consist- of phosphorus deficiency such as stiff sents a separate disease entity.
ently in the erythrocytes of New Zea- gait, creaking joints and chewing on In summary, PPH in North Ameri-
land cattle with PPH. Surveys indicate foreign objects were noted during the ca is typified by acute intravascular
that: a) the incidence of Heinz bodies is last 18 months of the study. A de- hemolysis, hemoglobinuria, anemia,
greater in PPH affected herds (29), b) creased erythrocyte count and hypo- and hypophosphatemia. Postpartum,
the prevalence of Heinz body anemia phosphatemia were reported in four high-producing dairy cows in their
is greater than the incidence of clinical cows which were fed a ration of sugar third to sixth lactation are most com-
hemoglobinuria (34) and c) the sever- beet leaves (6). Signs consistent with monly affected. Dietary phosphorus
ity of Heinz body anemia seems to PPH were observed in three of the four deficiency and/or rations containing
correlate with the degree of hypocu- cows. While able to duplicate the clini- cruciferous plants or beet products are
premia (35). Mechanisms for Heinz cal signs of PPH, these investigators suspected etiologies. The diagnosis of
body formation as a result of copper were unable to make definite conclu- PPH can be made on the basis of the
deficiency are speculative. Heinz sions because the number of test ani- history, clinical and laboratory find-
bodies are formed when irreversible mals was inadequate and control ani- ings and after eliminating other causes
oxidation causes precipitation of den- mals were not included. of intravascular hemolysis. The
atured hemoglobin. Superoxide dis- pathogenesis of red cell destruction is
mutase, a copper metalloenzyme, is CONCLUSIONS unknown. Recent reports in human
part of the erythrocyte's protective The papers from New Zealand are the beings and laboratory animals asso-
mechanism against oxidant stress. A most recently published material on ciating severe hypophosphatemia with
copper deficiency would likely depress PPH. The features of the disease in hemolytic anemia and with abnormal-
superoxide dismutase activity, com- New Zealand present a definite contrast ities in red cell metabolism suggest that
promise the erythrocyte's potential to to the syndrome observed in North a similar mechanism may be involved
withstand oxidative injury and cause America (Table II). Postparturient in PPH (41).
Heinz body formation (38). hemoglobinuria in New Zealand is a
Urinalysis can be helpful in the herd problem usually affecting younger ACKNOWLEDGM ENTS
diagnosis of PPH. Hemoglobinuria is cows. Copper deficiency and Heinz The authors wish to acknowledge the
the most remarkable clinical sign of body anemia, as features of PPH, have support of the Medical Research
PPH. Microscopic examination ofthe not been reported elsewhere. It is possi- Council of Canada, The Alberta Agri-
urine sediment is imperative to differ- ble that the Heinz bodies and the cultural Research Trust, Agriculture
entiate hematuria from hemoglobin- copper-deficient status of affected cows Canada and the Saskatchewan
uria. Ketones, bilirubin and protein have been overlooked by other investi- Department of Agriculture.
can be expected in the urine depending
on the course of the disease.
Most authors have reported very TABLE II
low levels of serum phosphorus (0.4- COMPARATIVE FEATURES OF PPH IN NORTH AMERICA
1.5 mg/dL) during the hemolytic cri- AND NEW ZEALAND
sis. In affected herds, lactating but
clinically normal cows have been North America New Zealand
moderately hypophosphatemic (2-3 Incidence sporadic herd problem: up to 40%
mg/ dL); nonlactating cows usually incidence
have normal serum phosphorus con- mortality: 10-50% mortality: occasional
centrations (14). Serum calcium con- Occurrence high-producing, adult younger cows
centration is usually normal and total cows
1st and 2nd lactation
3rd-6th lactation
bilirubin levels parallel the intensity of 24 weeks postpartum 2-4 weeks postpartum
clinical icterus (2,19). winter housing ryegrass pasture

EXPERIMENTATION Suspected Etiology phosphorus deficiency copper deficiency

cruciferous plants induced by excessive
Attempts to reproduce the disease or beet products molybdenum fertilization
under experimental conditions have Pathogenesis unknown diminished capacity of RBC
been successful. Hemoglobinuria was to withstand oxidant stress
observed in three of ten cows fed an Clinical Signs Similar
exclusive diet of rape over a period of Laboratory Findings regenerative anemia regenerative anemia
two to four weeks (9). One of the hemoglobinuria hemoglobinuria
affected animals was hypophos- serum phosphorus: low serum phosphorus:
phatemic. Hemoglobinuria did not usually normal
occur in a second experiment in which Heinz bodies
low levels of serum and
four cows were fed turnips. A diet of liver copper
alfalfa hay and dried beet pulp fed to parenteral copper
Treatment phosphate therapy
one cow for 32 months (three pregnan-

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REFERENCES 167-168. 31. CHASE LE. Mineral supplementation of var-
1. PENNY RHC. Post-parturient haemoglobinu- 16. HJARRE A. Die puerperale hamoglobinamie ious roughage diets for milking cows. In:
ria (haemoglobinaemia) in cattle. Vet Rec des rindes. Acta Pathol Microbiol Scand Proc Cornell Nutr Conf Feed Manufactur-
1956; 68: 238-241. 130; (Suppl) 7. ers 1976: 34-39.
2. MADSEN DE, NIELSEN HM. Parturient hemo- 17. PARKINSON B, SUTHERLAND AK. Post- 32. SMITH RH. S-methylcysteine sulphoxide, the
globinemia of dairy cows. J Am Vet Med parturient haemoglobinuria of dairy cows. Brassica anaemia factor. Vet Sci Comm
Assoc 1939; 94: 577-586. Aust Vet J 1954; 30: 232-236. 1978; 2: 47-61.
3. SCHOFIELD FW. Bovine hemoglobinuria 18. MALIK K, GAUTAM oP. Haemoglobinuria in 33. SMITH B, COUP MR. Hypocuprosis: A clinical
associated with an intestinal infection buffaloes. J Res HAU 1971; 1: 109-113. investigation of dairy herds in Northland. N
caused by the Cl. welchii. In: Rep Ont Vet 19. SCHOFIELD FW. Further studies in bovine Z Vet J 1973; 21: 252-258.
Coll 1933: 42-61. hemoglobinuria (red water), In: Rep Ont 34. SMITH B. Copper and molybdenum imbal-
4. HUNGERFORD TG. Diseases of livestock. Sid- Vet Coll 1938: 35-39. ance in relationship to post-paturient hae-
ney: Angus and Robertson, 1970: 274. 20. SJOBERG K. Blodets Kemiska sammansattn- moglobinuria in cattle. N Z Vet J 1973; 21:
5. FARQUHARSON J, SMITH KW. Post-parturient ing. II. Vid puerperal hamoglobinemi hos 240.
hemoglobinuria of cattle. J Am Vet Med not. Svenk Vet Tidskr 1938; 43: 335-345. 35. GARDNER DE, MARTINOVICH D, WOODHOUSE
Assoc 1938; 93: 37-39. 21. MADSEN DE, NIELSEN HM. The relationship of DA. Haematological and biochemical find-
6. FREUDENBERG F. Untersuchungen uber die parturient hemoglobinemia of dairy cows to ings in bovine post-parturient haemo-
puerperale hamoglobinurie des rindes. aphosphorosis. N Am Vet 1940; 21: 81-89. globinuria and the accompanying Heinz-
DTW 1955; 62: 422-429. 22. NATIONAL ACADEMY OF SCIENCES -National body anaemia. N Z Vet J 1976; 24: 117-122.
7. UDALL DH. The practice of veterinary medi- Research Council. Atlas of nutritional data 36. SMITH B. The effects of copper supplementa-
cine. 6th ed. Ithaca: Udall DH, 1954: on United States and Canadian feeds. tion on stock health and production. 1.
287-289. Washington DC, 1971. Field investigations into the effects of
8. MULLINS JC, RAMSAY WR. Haemoglobinuria 23. CLEGG FG, EVANS RK. Haemoglobinaemia of copper supplementation on stock health in
and anaemia associated with aphosphoro- cattle associated with the feeding of Brassi- dairy herds with a history of post-parturient
sis. Aust Vet J 1959; 35: 140-147. cae species. Vet Rec 1962; 74: 1169-1176. haemoglobinuria. N Z Vet J 1975; 23: 73-77.
9. SCHOFIELD FW. Nonspecific hemoglobinuria 24. WALLACE WR. Parturient hemoglobinuria of 37. SMITH B, WOODHOUSE DA, FRASER AJ. The
and acute pulmonary emphysema of cattle bovines. Vet Rec 1926; 6: 1035-1038. effects of copper supplementation on stock
as essential enterotoxemias. J Am Vet Med 25. GLAWISCHNIG E. Zur behandlung der peur- health and production. 2. The effect of par-
Assoc 1941; 96: 28-32. peralen hamoglobinurie des rindes. Wien enteral copper on incidence of disease, hae-
10. STAMP JT, STEWART J. Haemolytic anaemia Tieraerztl Mschr 1961; 48: 589-594. matological changes and blood copper lev-
with jaundice in sheep. J Comp Pathol 1953; 26. BARRIERE G. Puerperal haemoglobinaemia els in a dairy herd with hypocuprosis. N Z
63: 48-52. in cows. Encycl Vet Period 1964; 21: Vet J 1975; 23: 109-112.
11. AWAD Fl, EL-LATIF K. The first record of a 374-376. 38. CAPLE IW. Post-parturient hemoglobinuria.
disease condition in Egyptian Buffalo simu- 27. EL-LATIF K, AWAD Fl. Haemoglobinuria of In: Howard JL, ed. Current veterinary ther-
lating post-parturient haemoglobinuria. buffaloes associated with excessive feeding apy, food animal practice. Philadelphia:
Vet Rec 1963; 75: 298-300. of Tripholium alexandrinum (berseem). J WB Saunders, 1981: 355-357.
12. NAGPAL M, GAUTAM OP, GULATI RL. Haemo- Vet Sci UAR 1964; 1: 69-74. 39. GEERTSEMA G. Een toxische haemoglobi-
globinuria in buffaloes. Indian Vet J 1968; 28. DHILLON KS, SINGH J, BAJWA R. Treatment of naemie en haemoglobinurie bij het rund in
45: 1048-1959. haemoglobinuria due to molybdenum- Drenthe. Tijdschr Diergeneesk 1940; 64:
13. SETTY D, NARAYANA K. A case of non-febrile induced phosphorus deficiency in buffaloes: 176-185.
haemoglobinuria in a she goat. Indian Vet J A note. Indian J Anim Sci 1972; 42: 40. MADSEN DE, NIELSEN HM. The production of
1975; 52: 149. 996-998. parturient hemoglobinemia by low phos-
14. BLOOD DC, HENDERSON JA, RADOSTITS OM. 29. MARTINOVICH D, WOODHOUSE DA. Post- phorus intake. J Am Vet Med Assoc 1944;
Veterinary medicine. 5th ed. Philadelphia: parturient haemoglobinuria in cattle: A 105: 22-25.
Lea & Febiger, 1979: 862-863. Heinz body haemolytic anaemia. N Z Vet J 41. KNOCHEL iP. The pathophysiology and
15. TARR A. A note on the occurrence of puer- 1971; 19: 259-263. clinical characteristics of severe hypophos-
peral haemoglobinaemia of cattle in South 30. RAINEY jw. An acute case of parturient hae- phatemia. Arch Intern Med 1977; 137:
Africa. J S Afr Vet Assoc 1947; 188: moglobinuria. Aust Vet J 1945; 21: 73-74. 203-220.

RESEARCH GRANT APPLICATIONS INVITED

Applications are invited for grants in aid of research on animal diseases in
Canada. The deadline for receiving applications is November 30.
For further information and application forms contact:
The Secretary
Canadian Veterinary Research Trust Fund
339 Booth Street
Ottawa, Ontario Kl R 7K1

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