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Hematologic changes of pregnancy by trimester

Hematologic changes of pregnancy by trimester
  Nonpregnant* First trimester Second trimester Third trimester References
Hematology
Erythropoietin (units/L) 4 to 27 12 to 25 8 to 67 14 to 222 1 to 3
Ferritin (ng/mL) 10 to 150Δ 6 to 130 2 to 230 10 to 116 1 to 8
Folate, red blood cell (ng/mL) 150 to 450 137 to 589 94 to 828 109 to 663 6, 9, 10
Folate, serum (ng/mL) 5.4 to 18.0 2.6 to 15.0 0.8 to 24.0 1.4 to 20.7 1, 6, 9 to 13
Haptoglobin (mg/mL) 25 to 250 130 +/- 43 115 +/- 50 135 +/- 65 31
Hemoglobin (g/dL) 12.0 to 15.8Δ 11.0 to 13.9 10.6 to 14.8 9.5 to 15.0 2, 3, 6, 7, 13, 32
Hematocrit (%) 35.4 to 44.4 33.0 to 41.0 32.0 to 39.0 30.0 to 40.0 1, 2, 5, 6, 13 to 15, 32
Iron, total binding capacity (mcg/dL) 251 to 406 278 to 403 Not reported 359 to 609 7
Iron, serum (mcg/dL) 41 to 141 72 to 143 44 to 178 30 to 193 2, 7
Mean corpuscular hemoglobin (pg/cell) 27 to 32 30 to 32 30 to 33 29 to 32 5
Mean corpuscular volume (xm3) 79 to 93 81 to 96 82 to 97 81 to 99 5, 6, 13, 14
Platelet (x109/L) 165 to 415 174 to 391 155 to 409 146 to 429 5, 6, 14, 16, 17
Mean platelet volume (mcm3) 6.4 to 11.0 7.7 to 10.3 7.8 to 10.2 8.2 to 10.4 5
Red blood cell count (x106/mm3) 4.00 to 5.20Δ 3.42 to 4.55 2.81 to 4.49 2.71 to 4.43 5, 6, 13, 14
Red cell distribution width (%) <14.5 12.5 to 14.1 13.4 to 13.6 12.7 to 15.3 5
White blood cell count (x103/mm3) 3.5 to 9.1 5.7 to 13.6 5.6 to 14.8 5.9 to 16.9 5, 6, 13, 14, 18
Neutrophils (x103/mm3) 1.4 to 4.6 3.6 to 10.1 3.8 to 12.3 3.9 to 13.1 5, 14, 16, 18
Lymphocytes (x103/mm3) 0.7 to 4.6 1.1 to 3.6 0.9 to 3.9 1.0 to 3.6 5, 14, 16, 18
Monocytes (x103/mm3) 0.1 to 0.7 0.1 to 1.1 0.1 to 1.1 0.1 to 1.4 5, 14, 18
Eosinophils (x103/mm3) 0.0 to 0.6 0.0 to 0.6 0.0 to 0.6 0.0 to 0.6 14, 18
Basophils (x103/mm3) 0.0 to 0.2 0.0 to 0.1 0.0 to 0.1 0.0 to 0.1 14, 18
Transferrin (mg/dL) 200 to 400 254 to 344 220 to 441 288 to 530 4, 5
Transferrin, saturation without iron (%) 22 to 46 Not reported 10 to 44 5 to 37 3
Transferrin, saturation with iron (%) 22 to 46 Not reported 18 to 92 9 to 98 3
Coagulation
Antithrombin, functional (%) 70 to 130 89 to 114 78 to 126 82 to 116 17, 19, 20
D to dimer (mcg/mL) 0.22 to 0.74 0.05 to 0.95 0.32 to 1.29 0.13 to 1.70 17, 20 to 24, 30
Factor V (%) 50 to 150 75 to 95 72 to 96 60 to 88 25
Factor VII (%) 50 to 150 100 to 146 95 to 153 149 to 211 17
Factor VIII (%) 50 to 150 90 to 210 97 to 312 143 to 353 17, 25
Factor IX (%) 50 to 150 103 to 172 154 to 217 164 to 235 17
Factor XI (%) 50 to 150 80 to 127 82 to 144 65 to 123 17
Factor XII (%) 50 to 150 78 to 124 90 to 151 129 to 194 17
Fibrinogen (mg/dL) 211 to 496 244 to 510 291 to 538 301 to 696 5, 17, 20, 21, 23, 24, 30
Homocysteine (mmol/L) 4.4 to 10.8 3.34 to 11.00 2.0 to 26.9 3.2 to 21.4 6, 9, 10 to 12
International normalized ratio 0.90 to 1.04◊ 0.86 to 1.08 0.83 to 1.02 0.80 to 1.09 19, 24
Partial thromboplastin time, activated (seconds) 26.3 to 39.4 23.0 to 38.9 22.9 to 38.1 22.6 to 35.0 5, 17, 19, 24
Plasminogen activator inhibitor to 1 (PAI to 1) antigen (pg/mL) 17.3 ± 5.7 17.7 ± 1.9 Not reported 66.4 ± 4.9 30
Plasminogen activator inhibitor to 1 (PAI to 1) activity (arbitrary units) 9.3 ± 1.9 9.0 ± 0.8 Not reported 31.4 ± 3.0 30
Prothrombin time (seconds) 12.7 to 15.4 9.7 to 13.5 9.5 to 13.4 9.6 to 12.9 5, 17, 24
Protein C, functional (%) 70 to 130 78 to 121 83 to 133 67 to 135 19, 25, 26
Protein S, total (%) 70 to 140 39 to 105 27 to 101 33 to 101 17, 25, 26
Protein S, free (%) 70 to 140 34 to 133 19 to 113 20 to 65 25, 26
Protein S, functional activity (%) 65 to 140 57 to 95 42 to 68 16 to 42 25
Tissue plasminogen activator (ng/mL) 1.6 to 13.0§ 1.8 to 6.0 2.36 to 6.60 3.34 to 9.20 17, 19, 30
Tissue plasminogen activator inhibitor-1 (ng/mL) 4 to 43 16 to 33 36 to 55 67 to 92 17
von Willebrand measurements
von Willebrand factor antigen (%) 75 to 125 62 to 318 90 to 247 84 to 422 20, 27, 28
ADAMTS-13, von Willebrand cleaving protease 40 to 170¥ 40 to 160 22 to 135 38 to 105 20, 28
* Unless otherwise specified, all normal reference values are from the seventeenth edition of Harrison's Principles of Internal Medicine[29].
¶ Range includes references with and without iron supplementation.
Δ Normal reference range is specific range for females.
◊ Reference values are from Cerneca et al: Coagulation and fibrinolysis changes in normal pregnancy increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis[19].
§ References values are from Cerneca et al and Choi et al: Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy[17,19].
¥ Reference values are from Mannuci et al: Changes in health and disease of the metalloprotease that cleaves von Willebrand factor[28].
References:
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  3. Milman N, Graudal N, Nielsen OJ, Agger AO. Serum erythropoietin during normal pregnancy: Relationship to hemoglobin and iron status markers and impact of iron supplementation in a longitudinal, placebo-controlled study on 118 women. Int J Hematol 1997; 66:159.
  4. Larsson A, Palm M, Hansson LO, Axelsson O. Reference values for clinical chemistry tests during normal pregnancy. BJOG 2008; 115:874.
  5. Lockitch G. Handbook of Diagnostic Biochemistry and Hematology in Normal Pregnancy. CRC Press, Boca Raton, FL, 1993.
  6. Milman N, Bergholt T, Byg KE, et al. Reference intervals for haematological variables during normal pregnancy and postpartum in 434 healthy Danish women. Eur J Haematol 2007; 79:39.
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  8. van Buul EJ, Steegers EA, Jongsma HW, et al. Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; a longitudinal study. Neth J Med 1995; 46:73.
  9. Milman N, Byg KE, Hvas AM, et al. Erythrocyte folate, plasma folate and plasma homocysteine during normal pregnancy and postpartum: A longitudinal study comprising 404 Danish women. Eur J Haematol 2006; 76:200.
  10. Walker MC, Smith GN, Perkins SL, et al. Changes in homocysteine levels during normal pregnancy. Am J Obstet Gynecol 1999; 180:660.
  11. López-Quesada E, Vilaseca MA, Lailla JM. Plasma total homocysteine in uncomplicated pregnancy and in preeclampsia. Eur J Obstet Gynecol Reprod Biol 2003; 108:45.
  12. Ozerol E, Ozerol I, Gökdeniz R, et al. Effect of smoking on serum concentrations of total homocysteine, folate, vitamin B12, and nitric oxide in pregnancy: A preliminary study. Fetal Diagn Ther 2004; 19:145.
  13. Qvist I, Abdulla M, Jägerstad M, Svensson S. Iron, zinc and folate status during pregnancy and two months after delivery. Acta Obstet Gynecol Scand 1986; 65:15.
  14. Balloch AJ, Cauchi MN. Reference ranges for haematology parameters in pregnancy derived from patient populations. Clin Lab Haematol 1993; 15:7.
  15. Singh HJ, Mohammad NH, Nila A. Serum calcium and parathormone during normal pregnancy in Malay women. J Matern Fetal Med 1999; 8:95.
  16. Karim SA, Khurshid M, Rizvi JH, et al. Platelets and leucocyte counts in pregnancy. J Pak Med Assoc 1992; 42:86.
  17. Choi JW, Pai SH. Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy. Ann Hematol 2002; 81:611.
  18. Belo L, Santos-Silva A, Rocha S, et al. Fluctuations in C-reactive protein concentration and neutrophil activation during normal human pregnancy. Eur J Obstet Gynecol Reprod Biol 2005; 123:46.
  19. Cerneca F, Ricci G, Simeone R, et al. Coagulation and fibrinolysis changes in normal pregnancy increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997; 73:31.
  20. Lattuada A, Rossi E, Calzarossa C, et al. Mild to moderate reduction of a von Willebrand factor cleaving protease (ADAMTS-13) in pregnant women with HELLP microangiopathic syndrome. Haematologica 2003; 88:1029.
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  28. Mannucci PM, Canciani MT, Forza I, et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001; 98:2730.
  29. Kratz A, Pesce MA, Basner RC, Einstein AJ. Appendix: Laboratory values of clinical importance. In: Harrison's Principles of Internal Medicine, 18th ed, Longo DL, Fauci AS, Kasper DL, et al (Eds), McGraw-Hill, New York 2012.
  30. Hale SA, Sobel B, Benvenuto A, et al. Coagulation and fibrinolytic system protein profiles in women with normal pregnancies and pregnancies complicated by hypertension. Pregnancy Hypertens 2012; 2:152.
  31. Haram K, Augensen K, Elsayed S. Serum protein pattern in normal pregnancy with special reference to acute-phase reactants. Br J Obstet Gynaecol 1983; 90:139.
  32. Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency anemia in the United States. MMWR Recomm Rep 1998; 47:1.
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