16.5 Hematology: Erythropoiesis, Leukocytes, Platelets & Coagulation

16.5 Hematology: Erythropoiesis, Leukocytes, Platelets & Coagulation

The physiology outline lists hematology: coagulation, platelets, erythrocytes and leukocytes. This physiology explains anemia in the ischemic foot, perioperative bleeding risk and venous thromboembolism. Disorders are covered in 9.1 and 7.3, and the biochemistry of heme and hemoglobin in 18.4.

Hematopoiesis

Blood formation moves from the yolk sac to the fetal liver and spleen and then to the bone marrow. In adults it is concentrated in the axial skeleton and proximal long bones. Pluripotent stem cells give rise to myeloid progenitors (red cells, granulocytes, monocytes and platelets) and lymphoid progenitors.

Erythrocytes

• Structure: biconcave, anucleate, with no mitochondria. They rely on glycolysis for ATP and the hexose monophosphate shunt for NADPH (18.4).
• Lifespan and turnover: red cells live about 120 days and are removed mainly by splenic macrophages. Reticulocytes (newly released cells) are normally about 1%. A rising reticulocyte count shows that the marrow is responding to blood loss or hemolysis.
• Indices: MCV (size), MCH and MCHC (hemoglobin content) and RDW (variability) classify anemia (9.1).
• Iron balance: the body holds about 3–4 g of iron and loses only about 1 mg a day (more with menstruation). Absorption is regulated by hepcidin, and transport is by transferrin and storage as ferritin.

Oxygen Content and Delivery

$$C_aO_2 = 1.34 \times [\text{Hb}] \times S_aO_2 + 0.003 \times P_aO_2$$

Worked example. With hemoglobin 15 g/dL, SaO2 0.98 and PaO2 95 mmHg:

$$1.34 \times 15 \times 0.98 + 0.003 \times 95 \approx 19.7 + 0.3 = 20.0\ \text{mL O}_2\text{/dL}$$

If hemoglobin falls to 9 g/dL with the same saturation and PaO2, oxygen content drops to about 12.1 mL O2/dL, a decrease of roughly 40%. Anemia lowers oxygen delivery (cardiac output × CaO2) even though PaO2 and pulse oximetry stay normal. This matters for healing an ischemic ulcer or a fresh flap.

Leukocytes

Neutropenia (absolute neutrophil count below 500/µL) sharply raises the risk of bacterial and fungal infection and blunts pus formation (9.1). Leukemoid reactions are very high WBC counts with mature cells caused by severe infection, not leukemia.

Platelets and Primary Hemostasis

Platelets are anucleate fragments of megakaryocytes. Normal counts are about 150,000–450,000/µL, and each platelet lives about 7–10 days. About one-third are held in the spleen.

1. Vascular spasm from endothelin and neural reflexes.
2. Adhesion: platelet GPIb binds von Willebrand factor (vWF) on exposed subendothelial collagen.
3. Activation: release of ADP and calcium from dense granules and vWF and fibrinogen from alpha granules, plus synthesis of thromboxane A2 (COX-1). Activation turns on GPIIb/IIIa.
4. Aggregation: GPIIb/IIIa cross-links platelets through fibrinogen to form the platelet plug.

Drugs at each step: aspirin (COX-1, 11.3), P2Y12 inhibitors such as clopidogrel (ADP receptor, 10.4) and GPIIb/IIIa inhibitors. von Willebrand disease, the most common inherited bleeding disorder, causes mucocutaneous bleeding and prolonged bleeding after procedures; desmopressin releases stored vWF in many patients. Spontaneous bleeding becomes a concern below about 10,000–20,000/µL. A count of about 50,000/µL or higher is a common minimum before surgery.

Secondary Hemostasis: The Coagulation System

Classic laboratory pathways still guide test interpretation: PT measures the extrinsic and common pathways (factor VII, X, V, II, fibrinogen) and aPTT measures the intrinsic and common pathways (XII, XI, IX, VIII) (8.4). In the body, coagulation follows the cell-based model:

1. Initiation: tissue factor on subendothelial cells binds factor VIIa and activates small amounts of IX and X, producing a little thrombin.
2. Amplification: this thrombin activates platelets and factors V, VIII and XI.
3. Propagation: on the activated platelet surface, the tenase complex (IXa-VIIIa) and prothrombinase complex (Xa-Va) produce a thrombin burst.
4. Fibrin formation: thrombin cleaves fibrinogen to fibrin, and factor XIIIa (a transglutaminase) cross-links it into a stable clot.

Vitamin K is required for gamma-carboxylation of factors II, VII, IX and X and proteins C and S (18.4); warfarin blocks this step (10.4). Calcium and phospholipid surfaces are needed for the complexes to assemble.

Natural Anticoagulants and Fibrinolysis

Factor V Leiden resists activated protein C (7.3), illustrating how loss of a natural brake promotes venous thrombosis after lower extremity immobilization.

Blood Groups and Transfusion

The ABO system has naturally occurring IgM antibodies against absent antigens. Type O red cells are the universal donor cells, and AB plasma is the universal donor plasma. Rh(D)-negative people make anti-D only after exposure. An ABO-incompatible transfusion causes an acute hemolytic reaction (Type II hypersensitivity) with fever, hemoglobinuria, hypotension and DIC.