Avian Hematology
In commercial poultry farming, serology plays a pivotal role in monitoring and disease diagnosis and the hematology assays rarely used for etiological diagnosis. In addition to this, avian hematological diagnosis has some constrains like small blood volume, the fragility of erythrocytes and hemolysis in EDTA anticoagulant, and staining variations with traditional Giemsa or Wright’s stains.
But hematological evaluation of avian species nevertheless can be used to evaluate health and well beings of poultry, prognosis of disease and the therapeutic responses. Since last 15 years or so, significant advances have been made in the field of avian hematology parallel to other areas like nutrition, therapeutics, wellness examinations, and surgery. Chicken is generally used as research animal model for other avian species.3.6.1 Properties of Blood
3.6.1.1 BloodVolume
The blood volume usually ranges from 6 to 11 mL/100 kg body weight and 10% of total blood volume and can be collected safely.
3.6.1.2 The Specific Gravity and the Viscosity
The specific gravity and the viscosity of the blood of different avian species are given in Table 4.28.
The higher viscosity in male may be due to higher number of cells compared to female.
The rate of sedimentation of erythrocytes usually depends upon the cell size, specific gravity of plasma and composition of plasma by governed by the gravitational force and the functional resistance of the surrounding plasma.
3.6.1.3 Hematocrit
The hematocrit values of different avian species are given in Table 4.29.
Table 4.28 The specific gravity and the viscosity of whole blood and plasma in different avian species
| Species | Specific gravity | Viscosity | ||
| Whole blood | Plasma | Whole blood | Plasma | |
| Chicken (female) | 1.050 | 1.099 | 3.08 | 1.51 |
| 1.054 | 1.021 | 3.67 | 1.42 | |
| Duck | 1.056 | 1.020 | 4.0 | 1.5 |
| Goose | 1.050 | 1.021 | 4.6 | 1.5 |
| Ostrich | 1.063 | 1.022 | 4.5 | - |
Source: Sturkie (1986)
Table 4.29 The hematocrit value of different avian species
| Species | Hematocrit value (%) |
| Chicken (sexually immature male) | 29 |
| Chicken (sexually immature female) | 29 |
| Chicken (sexually mature male) | 45 |
| Chicken (sexually mature female) | 29 |
| Turkey (male) | 45.1 |
| Turkey (male) | 36.4 |
| Ducks (mallard) | 43 |
| Quail | 38 |
| Pigeon | 52 |
Source: Sturkie (1986)
Sex has no significant influence on the hematocrit value in birds but inter species variations are evident.
An increase in hematocrit or hemo-concentration is induced by the release of epinephrine or hyperthermia.3.6.2 Composition of Plasma
The plasma of avian species is straw yellow in color and slightly turbid in appearance. The plasma contains 80% of water along with some dissolve substances like glucose, proteins, fatty acids, vitamins, minerals, and hormones (Table 4.30). The composition varies according to sex, age, egg production, food consumption, and physiological state of birds. Unlike mammals the colloidal osmotic pressure of avian plasma depends primarily on electrolytes (95%) followed by glucose, amino acids, urea (5%), and plasma proteins (0.5%).
Plasma proteins: The females have higher plasma proteins than males due to the egg production. The plasma proteins of the avian species are classified into three categories based on electrophoretic mobility namely pre-albumin, albumin, and globulin. The pre-albumin is also called as trans-thyrectin due to its thyroid-binding ability. Albumin is involved in facilitating nutrient transport (mainly fatty
Table 4.30 The composition of plasma in avian species
| Plasma constituents | Concentrations |
| Proteins (g/L) | 39.6 ± 0.74 |
| Albumin (g/L) | 15.9 ± 0.55 |
| Globulin (g/L) | 18.8 ± 0.96 |
| Glucose (mM/L) | 15.9 ± 0.32 |
| Sodium (mEq/L) | 152.5 ± 1.13 |
| Sodium (mEq/L) | 112.6 ± 1.28 |
| Calcium (mEq/L) | 2.56 ±0.10 |
| Sodium (mEq/L) | 3.21 ± 0.19 |
| Uric acid (mM/L) | 0.50 ± 0.04 |
| Blood urea nitrogen (mM/L) | 1.11 ± 0.09 |
Source: Sturkie (1986)
acids) and lipophilic hormones.
The concentration of plasma albumin varies with the state of birds. Plasma albumin concentrations are reported to be decreased in laying females. Diurnal variations in the plasma albumin were also reported. Feed withdrawal and reduced photoperiod also reduce the albumin concentration. The globulins are more concentrated in birds compared to mammals; thus, birds are good antibody producers. There are three types of immunoglobulins in birds like IgA (0.3 g/L), IgM (2.7 g/L), and IgY (5.5 g/L). Immunoglobulin Y is equivalent to IgG in mammals. The globulin concentration is increased during reduced photoperiod and feed withdrawal. In layer birds, IgY are reported to be lower due to the transportation of circulating IgY into the yolk. In male chicken, α1-globulin concentration declines during growth.Plasma lipids: The plasma of layer birds contains higher lipids (two to five-folds increase) when compared to non-laying hens.
Plasma glucose: The plasma glucose concentration is higher in birds compared to mammals. Alterations in the glucose concentration increases with hatching.
Plasma electrolytes: The calcium concentration in laying birds are more (two-folds increase) than non-laying birds. Plasma concentration of sodium and potassium are decreased during acute heat stress in chicken. In birds, urates or uric acid is one of the predominate components of plasma which are the catabolic end products of protein and non-protein.
Plasma enzymes: A number of enzymes namely alkaline phosphatase (ALP), glutamic oxaloacetic ransaminase (GOT), asparate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), cholinesterase, creatine phosphotransferase, and lactic acid dehydrogenase (LDH) are evident in the plasma of birds depending on the physiological state of the birds. In dehydration and hyperthermia, SGPT is elevated. In feed restriction, SGPT is decreased and LDH, GOT, and ALP are increased. In organophosphorus poisoning, plasma cholinesterase activity was decreased and thus it is used as bio-markers in wildlife risk assessment.
4.6.3 Erythrocytes
Unlike mammals, the circulating erythrocytes of avian species are ovoid in shape with a centrally located round nuclei and mitochondria. The morphometric characteristics of avian erythrocytes along with hemoglobin content are summarized in Table 4.31.
The Na+/K+/2Cl- cotransporters in the avian erythrocytes are involved in the transport of sodium and potassium across
Table 4.31 The morphometric characteristics of avian erythrocytes along with hemoglobin content
| Parameters | Value |
| Total erythrocyte counts (106/pL) | 3.2 |
| Hemoglobin (%) | 10.1 |
| Erythrocyte volume (fL) | 149.4 |
| Erythrocyte length (μm) | 12.2 |
| Erythrocyte width (μm) | 7.1 |
| Erythrocyte cross sectional area (μm2) | 68.0 |
Source: Sturkie (1986)
the erythrocyte membrane. There is higher sodium efflux in turkey erythrocytes compared to mammals. The erythrocytes potassium transport is decreased with age in avian species.
The total erythrocyte counts varied significantly between seasons with the highest in fall compared to winter and spring. Diurnal variations in erythrocyte counts are also noticed in birds. The total erythrocyte count is usually high and mid night and low around noon.
Hemoglobin is the most abundant protein inside the erythrocytes. The nuclei of avian erythrocytes also contain hemoglobin transported across the pores of nuclear membrane.
The nuclei of avian erythrocyte contain condensed chromatin associated with histones (responsible for control of transcription, DNA replication, and repair). Despite of the presence of nuclei, avian erythrocytes are unable to divide.
4.6.3.1 Erythrocyte Metabolism
The major metabolic fuel of avian erythrocytes is glucose though the entry of glucose in avian erythrocytes is low due to small number of GLUT1 (200 copies of GLUT1 per erythrocyte compared to 300,000 in humans). Chicken erythrocytes can use glycine as a substrate for energy metabolism.
The major metabolic pathway is the TCA cycle due to the presence of mitochondria. During the early embryonic life, avian erythrocytes contain high ATP concentrations along with cytidine triphosphate (CTP) and Uridine-5,-triphosphate (UTP). Another interesting feature of avian erythrocytes is the high amount of 2,3-BPG during embryonic life that increases the oxygen affinity during embryonic life.
4.6.3.2 Erythropoiesis
The site of avian erythropoiesis in the bone marrow and liver is the major site for extramedullary hematopoiesis. However, the bone marrow decreases during the development of bone air sacs. The erythroid, lymphoid, and thrombocyte precursor cells start around 2-3 days of embryonation in the para-aortic region. The hematopoiesis is a two-stage process, in stage I, PHSCs are differentiated from early mesoderm and in stage II, these cells undergo further differentiation to form committed stem cell lineages like burst-forming unit (BFU) and colony-stimulating
| Table 4.32 The lifespan avian erythrocytes | |
| Species | Lifespan (days) |
| Ducks | 42 |
| Chicken | 35 |
| Pigeon | 48 |
| Quail | 34 |
Source: Sturkie (1986)
factors. Different developmental stages of avian erythrocytes are rubriblasts (or erythroblasts), prorubricytes, basophilic rubricytes, early polychromatic rubricytes, late polychromatic rubricytes, polychromatic rubricytes, and late polychromatic rubricytes.
Around 1-5% of circulating erythrocytes are late polychromatic rubricytes. The cells resemble mature erythrocytes with large size with more basophilic cytoplasm and less chromatin condensation.4.6.3.3 Lifespan of Erythrocytes
The lifespan of avian erythrocytes is less compared to mammals. This is probably due to higher body temperature, rapid metabolic rate due to consumption of more oxygen and nutrients than mammals. The lifespan of erythrocytes in different avian species have been presented in Table 4.32.
4.6.4 Hemoglobin
The hemoglobin of avian species is a tetrameric protein containing four polypeptide chains and heme unit with iron (Fe2+) at the center. In chicken, six forms of hemoglobin are available summarized in Table 4.33.
Avian Hbs exist in more tense (T) conformation than the mammalian Hbs and thus have lower oxygen affinity and higher thermal stability compared to mammalian Hb. Another striking difference between mammalian and avian hemoglobin is that the avian hemoglobin binds more with inositol pentaphosphate (IP5) unlike 2,3 BPG in mammalian Hb.
Know More.......
The birds fly at high altitude (bar-headed goose and Andean goose) and emperor penguins have higher oxygen affinity due to single substitutions in α-globin chains of hemoglobin.
4.6.5 Leukocytes
The total leukocyte count in chicken is 20-30 ? 103 cells/pL. Lymphocytes constitute largest proportion (55-60%) of blood, followed by heterophils (20-30%), monocytes (10%), eosinophils (3-8%), and basophils (1-4%). The heterophils of ostrich and pheasants is about 60-70%. Heterophils are analog of mammalian neutrophils with a diameter of 10-15 μm. The nucleus of heterophils also polymorphic with varying degree of lobulation. The cytoplasm of heterophils contains a characteristic rod-like granules.
4.6.6 Hemostasis in Avian Species
The clotting time of avian species is relatively more compared to mammals, hence avian blood clots slowly compared to mammals. The coagulation proteins are evolved from common ancestor. The overall coagulation mechanism is also same for mammals and birds.
Thrombocytes: Thrombocyte counts of the avian species usually range from 20,000 to 30,000/pL and may extend up to 50,000/pL. Avian thrombocytes are irregular in shape with pseudopodia. Intracellular organelles include mitochondria, endoplasmic reticulum, dense granules, and microtubules.
Table 4.33 Different forms of hemoglobin in avian species
| Stages of development | Forms of hemoglobin | Structure | Remarks |
| Embryonic | Major forms | Hb P (π, α, β, and ρ globin) | The highest concentration of major Hb forms is around fourth days of embryonic development and decreases gradually and become undetectable from 15 days. |
| Hb P' | |||
| Minor forms | HbM(αD globin) | Peak level is seen around 6-7 days and then decrease, but still persists up to hatching. | |
| HbE(αA globin) | |||
| Adult | Major forms | Hb A (αA2β2 globin) | |
| Minor forms | Hb D (αD2β2 globin chain) |
4.6.7 Blood Groups and Blood Transfusion
About 28 blood groups have been identified in domestic chicken under three different blood group systems (B, L, and N).
Blood transfusion is rarely practiced in avian species. The general indications for blood transfusion in birds are hypovolemic shock, acute hemorrhage, and coagulopathies in rodenticide poisoning. Blood transfusion is usually advocated when there is loss of 20% blood volume and a PCV level below 20%. The homologous transfusion is preferred in avian species. However, the first heterologous transfusion can safely be done as the birds lack preformed antibodies against blood group antigens. The mean half-life of erythrocytes in homologous transfusion is more (7 days) compared to heterologous transfusion (12 h) studied in pigeon (Sandmeier et al. 1994).
Learning Outcomes
• Blood: Blood is a fluid connective tissue comprising plasma and blood corpuscles. There are three types of blood corpuscles viz. red blood corpuscles (RBC), white blood corpuscles (WBC), and platelets. Blood plasma facilitates free movements of blood corpuscles. Varies inorganic and organic components constitute the plasma. Plasma protein and plasma lipids perform variety of functions. RBCs are concerned with gaseous transport. The main function of WBC is to provide immunity. Platelets are involved in blood coagulation process. Other than gaseous transport, blood facilitates nutrient transport, buffering action, thermoregulation, excretion of metabolic waste products, and transport medium of hormones and drugs.
• Hematopoiesis: Hematopoiesis is the formation of blood cells. It starts during embryonic development from mesodermal germ layer and continued throughout adulthood to produce and replenish the blood cellular components. The precursors of all blood cells are pluripotential hematopoietic stem cells (PHSC) characterized by their long selfrenewal capacity and pluripotency. PHSCs are differentiated into common myeloid progenitors (CMP) or colony forming unit granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM), and common lymphoid progenitor (CLP). CMP generates megakaryocyte, erythroid, granulocytes, and macrophages progenitors and CLP give rise to B and T lymphocytes. The platelets are derived from megakaryocytes. The generation of RBC, WBC, and platelets are termed as erythropoiesis, leucopoiesis, and thrombopoiesis, respectively.
• Iron metabolism: Iron is an integral component of hemoglobin, myoglobin, and other substances such as cytochrome, cytochrome oxidase, peroxidase, and catalase. In the body, iron mainly exists either in the form of hemoprotein and non-heme iron. The metabolism of iron is regulated by iron reserve in the body, hypoxia, and rate of erythropoiesis.
• Hemoglobin: Hemoglobin is an iron containing conjugated protein composed of heme (non-protein prosthetic group) and globin exclusively found in erythrocytes and transports the oxygen from lungs to tissues and carbon-dioxide from tissues to lungs. The synthesis of hemoglobin begins in the pro-erythroblast stage and continues till the reticulocyte stage. Hemoglobin forms different derivatives by combining with different molecules.
• Blood coagulation: It is cascade of enzyme activation which enables the stoppage of bleeding from injured vessels. The coagulation machinery includes clotting factors of the plasma, vascular endothelium, and platelets. The blood coagulation is divided into two broad events namely primary hemostasis in which there is the formation of weak platelet plug and secondary hemostasis where the reinforce of primary hemostasis is occurred with fibrin. The fibrinolytic mechanism facilitates dissolution of clots.
• Blood grouping: The determinants of blood groups are the specific polymorphic antigens that reside on the surface of erythrocytes (agglutinogens) and the antibodies (agglutinogens) present in the plasma. Different animals have different blood groups. Blood grouping and cross matching are essentially required from blood transfusion.
• Hematological disorders: Hematologic disorders are occurred due to pathological conditions of blood components and blood-forming organs. Hematologic diseases include genetic disorders, anemia, diseases of leukocytes, coagulation abnormalities, and transfusion hazards. Different pathogens and nutritional deficiencies are also predisposing factors for hematological disorders.
(continued)
• Avian hematology: The avian species have small blood volume, higher fragility of erythrocytes and staining variations. Unlike mammals, the circulating erythrocytes of avian species are ovoid in shape with a centrally located round nuclei and mitochondria. In chicken, six forms of hemoglobin are available. Lymphocytes constitute largest proportion of WBC, followed by heterophils, monocytes, eosinophils, and basophils. The clotting time of avian species is relatively more compared to mammals.
Exercises
Objective Questions
Q1. Property which allows erythrocytes to adhere with each other like the stack of coins known as
Q2. Which plasma protein helps in heme transport is?
Q3. The shape of erythrocytes of deer and antelope?
Q4. By which metabolic pathway mature RBCs produce 2,3-diphosphoglycerate (2,3-DPG)?
Q5. The third wave of hematopoiesis occurred in region of the developing embryo.
Q6. What is the name of cellular oxygen sensor that induces the secretion of erythropoietin in response to hypoxia?
Q7. Heme iron is absorbed more readily than non-heme iron—(True/False).
Q8. What is the predominant source of hepcidin?
Q9. The type of hemoglobin used to monitor hyperglycemia is.
Q10. Sulfhemoglobinemia occurred ___________________
infection.
Q11. What is the “eat-me” signals of erythrocyte destruction?
Q12. Monocytes are the largest leukocytes—(True/False).
Q13. Eicosanoid synthesized from vascular endothelium and prevents platelet aggregation is.
Q14.____________________________ species have no
universal donor.
Q15. What preservative component is used in blood to prevent decrease in 2,3 DPG?
Q16. Name the clinical condition that leads to the loss of erythrocyte biconcavity.
Q17. The movement of leukocytes to the injured tissues in response to bacterial toxins is called
Q18. Which avian immunoglobulin is analogous to mammalian IgG?
Q19. What are the avian leukocytes analogous to mammalian neutrophil?
Q20. Avian Hbs exists in more tense (T) conformation than the mammalian Hb—(True/False).
Subjective Questions
Q1. “Hypo-albuminemia leads to edema”—Justify the statement.
Q2. Why chronic renal failure leads to anemia?
Q3. In what condition methemoglobin is used as medication?
Q4. Why in Vit-12 deficiencies microcytic anemia occurs?
Q5. Why physiological polycythemia is common in high altitude animals?
Q6. What are the unique features of PHSC?
Q7. What are the advantages of erythrocyte bi-concavity?
Q8. What are the non-phagocytic defense strategies of neutrophils against pathogens?
Q9. What is the fate of hemoglobin in intravascular hemolysis?
Q10. What are T lymphocyte subsets?
Q11. Write down in brief about the fibrinolytic mechanism.
Q12. What do you mean by ontogeny of Hemoglobin Synthesis.
Q13. How intact vascular endothelium prevent coagulation in vitro?
Q14. What is respiratory burst?
Q15. Write down the difference between extravascular and intravascular hemolysis.
Answer to Objective Questions
A1. Rouleaux
A2. Hemopexin
A3. Sickle shaped
A4. Luebering-Rapoport pathway
A5. Aorta-gonad-mesonephros
A6. Hypoxia-inducible transcription factor-1
A7. True
A8. Hepatocytes
A9. Glycosylated hemoglobin
A10. Clostridium welchii
A11. Phosphatidyl serine
A12. True
A13. Prostacyclin
A14. Feline
A15. Inosine
A16. Spherocytosis
A17. Chemotaxis
A18. Immunoglobulin Y
A19. Heterophil
A20. True
Keywords for Answer to Subjective Questions
A1. Albumin, colloidal osmotic pressure of blood
A2. Kidney, erythropoietin, erythropoiesis
A3. Cyanide poisoning, methemoglobin, cyan-met hemoglobin
A4. Vit B12, DNA synthesis, Cell division
A5. High altitude, PO2, hypoxia, erythropoietin,
erythropoiesis
A6. Pluripotency, self-renewal
A7. Osmotic fragility, diffusion distance
A8. NETosis, Neutrophil-derived microparticles
A9. Hemoglobin, haptoglobin, bilirubin, liver
A10. Helper, cytotoxic, regulatory, surface marker
A11. Tissue type plasminogen activator, urokinase type plasminogen activator. Plasmin
A12. Switching of fetal to adult hemoglobin, alpha globin gene, beta globin gene
A13. Negativity, Prostacyclin (PGI2), Nitric oxide, Plasminogen activators
A14. Oxygen-dependent phagocytic killing
A15. Site, mechanism, fate of hemoglobin
Further Reading
Books
Blackmer J, Parish S (2002) Diseases caused by allogeneic incompatibilities. In: Smith BP (ed) Large animal int. med, 3rd edn. St. Louis, MO, Mosby Elsevier Science, pp 1604-1613
Campbell TW (1995) Avian hematology and cytology, 2nd edn. Iowa State University Press, Ames
Mayer J, Donnelly TM (2013) Clinical veterinary advisor: birds and exotic pets, vol 63043. Elsevier, St. Louis, Mo. https://doi.org/10. 1016/B978-1-4160-3969-3.00425-X
Reece WO (2015) The composition and functions of blood. In: Uemura EE (ed) Section II: Body fluids and homeostasis of Dukes’ physiology of domestic animals, 13th edn. Wiley Blackwell, Iowa, p 122
Sturkie PD (1986) Avian physiology. Springer, New York
Wakenell PS (2010) Hematology of chicken and turkey. In: Weiss DS, Wardrop KJ (eds) Schalm’s veterinary hematology, 6th edn. Blackwell Publishing, pp 958-966
Weiss DJ, Wardrop KJ (2010) Schalm’s veterinary hematology, 6th edn. Wiley-Blackwell, Iowa
Research Articles
Adili N, Melizi M, Belabbas H (2016) Species determination using the red blood cells morphometry in domestic animals. Vet World 9(9): 960-963
Blais MC, Berman L, Oakley DA, Giger U (2007) Canine Dal blood type: a red cell antigen lacking in some Dalmatians. J Vet Intern Med 21(2):281-286
Euler CC, Lee JH, Kim HY, Raj K, Mizukami K, Giger U (2016) Survey of two new (Kai 1 and Kai 2) and other blood groups in dogs of North America. J Vet Intern Med 30(5):1642-1647
Ferreira CN, Sousa MO, Dusse LMS, Carvalho MG (2010) A cell-based model of coagulation and its implications. Rev Bras Hematol Hemoter 32(5):416-421
Finnegan VM, Daniel GB, Ramsey EC (1997) Evaluation of whole blood transfusions in domestic pigeons (Columba livia). J Avian Med Sur 11(1):7-14
Goulet S, Giger U, Arsenault J, Abrams-Ogg A, Euler CC, Blais MC (2017) Prevalence and mode of inheritance of the Dal blood group in dogs in North America. J Vet Intern Med 31(3):751-758
Ivanov IT, Paarvanova BK (2021) Differential dielectroscopic data on the relation of erythrocyte membrane skeleton to erythrocyte deformability and flicker. Eur Biophys J 50:69-86. https://doi.org/ 10.1007/s00249-020-01491-4
Janyamethakul T, Sripiboon S, Somgird C, Pongsopawijit P, Panyapornwithaya V, Klinhom S, Loythong J, Thitaram C (2017) Hematologic and biochemical reference intervals for captive Asian elephants (Elephas maximus) in Thailand. Kafkas Univ Vet Fak Derg 23(4):665-669
Kaneko JJ, Harvey JW, Bruss ML (1997) Clinical biochemistry of domestic animals, 5th ed. Academic Press, San Diego, California. ISBN 0-12-396305-2
Klaassen JK (1999) Reference values in veterinary medicine. Lab Med 30(3):194-197
Lee JH, Giger U, Kim HY (2017) Kai 1 and Kai 2: characterization of these dog erythrocyte antigens by monoclonal antibodies. PLoS One 12(6):e0179932. https://doi.org/10.1371/journal.pone.0179932
Maas M, Keet DF, Nielen M (2013) Hematologic and serum chemistry reference intervals for free-ranging lions (Panthera leo). Res Vet Sci 95:266-268
Moras M, Lefevre SD, Ostuni MA (2017) From erythroblasts to mature red blood cells: organelle clearance in mammals. Front Physiol (Abs) 8:1076. https://doi.org/10.3389/fphys.2017.01076
Oishi T (1977) Blood groups and serum protein polymorphism in pigs and their application as genetic. Markers 11(3):179-185
SandmeierP, StauberEH, Wardrop KJ, Washizuka A (1994) Survival of pigeon red blood cells after transfusion into selected raptors. J Am Vet Med Assoc 204(3):427-429
Sankaran VG, Orkin SH (2013) The switch from fetal to adult hemoglobin. Cold Spring Harb PerspectMed 3(1):a011643
Schepelmann K (1990) Erythropoietic bone marrow in the pigeon: development of its distribution and volume during growth and pneumatization of bones. J Morph 203:21-34
Shrivastav AB, Singh KP (2012) Tigers blood: haematological and biochemical studies. Blood Cell. https://doi.org/10.5772/50360
Siah CW, Ombiga J, Adams LA, Trinder D, Olynyk JK (2006) Normal iron metabolism and the pathophysiology of iron overload disorders. Clin Biochem Rev 27(1):5-16
Stormont C, Suzuki Y, Rhode E (1964) Serology of horse blood groups. Cornell Vet 54:439-452
Thon J, NandItaliano JE (2010) Platelet formation. Semin Hematol 47(3):220-226
Weisel JW, Litvinov RI (2017) Fibrin formation, structure and properties. Sub Cell Biochem 82:405-456
Wienert B, Martyn GE, Funnell APW, Quinlan KGR, Crossley M (2018) Wake-up sleepy gene: reactivating fetal globin for β-hemoglobinopathies. Trends Genet 34(12):927-940