Plasma.

Approximately 55% of blood is plasma (Fig. 30-2). Plasma is composed primarily of water, but it also contains proteins, electrolytes, gases, nutrients (e.g., glucose, amino acids, lipids), and waste. The term serum refers to plasma minus its clotting factors. Plasma proteins include albumin, globulin, and clotting factors (mostly fibrinogen). Most plasma proteins are produced by the liver, except for antibodies (immunoglobulins), which are produced by plasma cells. Albumin is a protein that helps maintain oncotic pressure in the blood.¹

Blood Cells.

About 45% of the blood (see Fig. 30-2) is composed of formed elements, or blood cells. The three types of blood cells are erythrocytes (RBCs), leukocytes (WBCs), and thrombocytes (platelets). The primary function of erythrocytes is oxygen transportation, whereas the leukocytes are involved in protecting the body from infection. Platelets promote blood coagulation.

Vascular Response.

When a blood vessel is injured, an immediate local vasoconstrictive response occurs. Vasoconstriction reduces the leakage of blood from the vessel not only by restricting the vessel size but also by pressing the endothelial surfaces together. The latter reaction enhances vessel wall stickiness and maintains closure of the vessel even after vasoconstriction subsides. Vascular spasm may last for 20 to 30 minutes, allowing time for the platelet response and plasma clotting factors to be activated. The platelet response and plasma clotting factors are triggered by endothelial injury and the release of substances such as tissue factor (TF).¹

Platelet Plug Formation.

Platelets are activated when they are exposed to interstitial collagen from an injured blood vessel. Platelets stick to one another and form clumps. The stickiness is termed adhesiveness, and the formation of clumps is termed aggregation or agglutination. This interaction causes the platelets to release substances such as platelet factor 3 and serotonin, which facilitate coagulation. At the same time, platelets release adenosine diphosphate, which increases platelet adhesiveness and aggregation, thereby enhancing the formation of a platelet plug. In addition, von Willebrand factor (vWF) is important in forming an adhesive bridge between platelets and vascular subendothelial structures. It is synthesized in endothelial cells and megakaryocytes and acts as a carrier for factor VIII.

In addition to their independent contribution to clotting, platelets also facilitate the reactions of the plasma clotting factors. As Fig. 30-4 shows, platelet lipoproteins stimulate necessary conversions in the clotting process.

Plasma Clotting Factors.

The formation of a visible fibrin clot on the platelet plug is the conclusion of a complex series of reactions involving different clotting (coagulation) factors. The plasma clotting factors are labeled with both names and Roman numerals (Table 30-2). Plasma proteins circulate in inactive forms until stimulated to initiate clotting through one of two pathways, intrinsic or extrinsic (see Fig. 30-4). The intrinsic pathway is activated by collagen exposure from endothelial injury when the blood vessel is damaged. The extrinsic pathway is initiated when tissue factor or tissue thromboplastin is released extravascularly from injured tissues.

Regardless of whether clotting is initiated by substances internal or external to the blood vessel, coagulation ultimately follows the same final common pathway of the clotting cascade. Thrombin, in the common pathway, is the most powerful enzyme in the coagulation process (see Fig. 30-4). It converts fibrinogen to fibrin, which is an essential component of a blood clot.

Lysis of Clot.

Just as some blood elements foster coagulation (procoagulants), others interfere with clotting (anticoagulants). This counter mechanism to blood clotting serves to keep blood in its fluid state. Anticoagulation may be achieved by antithrombin activity, vessel and platelet activity, and fibrinolysis. As the name implies, antithrombins keep blood in a fluid state by antagonizing thrombin, a powerful coagulant. Endogenous heparin, antithrombin III, protein C, and protein S are examples of anticoagulants.

The second means of maintaining blood in its fluid form is fibrinolysis, a process resulting in the dissolution of the fibrin clot. The fibrinolytic system is initiated when plasminogen is activated to plasmin (Fig. 30-5). Thrombin is one of the substances that can activate the conversion of plasminogen to plasmin, thereby promoting fibrinolysis. The plasmin attacks either fibrin or fibrinogen by splitting the molecules into smaller elements known as fibrin split products (FSPs) or fibrin degradation products (FDPs). (More information about FSPs can be found in Table 30-7 later in this chapter and in the discussion of disseminated intravascular coagulation in Chapter 31.)

If fibrinolysis is excessive, the patient is predisposed to bleeding. In such a situation, bleeding results from the destruction of fibrin in platelet plugs or from the anticoagulation effects of increased FSPs. Increased FSPs lead to impaired platelet aggregation, reduced prothrombin, and an inability to stabilize fibrin.

Past Health History.

It is important to learn whether the patient has had prior hematologic problems. Specifically ask about previous problems with anemia, bleeding disorders, and blood diseases such as leukemia. Also document other related medical conditions such as malabsorption or liver (e.g., hepatitis, cirrhosis), kidney, or spleen disorders. Patients may have received a kidney transplant, may have lost a spleen to traumatic injury, or may have a history of IV drug or alcohol use that affects their risk for hematologic disorders. A history of recent or recurrent infections or problems with blood clotting is also important to note.

Medications.

A complete medication history of prescription and over-the-counter drugs is an important component of a hematologic assessment. Specifically address the use of vitamins, herbal products, or dietary supplements because many patients may not consider them to be drugs. Many drugs may interfere with normal hematologic function (see eTable 30-1 available on the website for this chapter).12–14 Herbal therapy can interfere with clotting (see Complementary & Alternative Therapies box in Chapter 38 on p. 851). Antineoplastic agents used to treat malignant disorders (see Chapter 16) and antiretroviral agents used to treat human immunodeficiency virus (HIV) infection (see Chapter 15) may cause bone marrow depression. A patient previously treated with chemotherapy agents, particularly alkylating agents, has a higher risk of developing a secondary malignancy of leukemia or lymphoma. A patient on long-term anticoagulant therapy such as warfarin (Coumadin) could be at risk for bleeding problems.

Surgery or Other Treatments.

Ask the patient about specific past surgical procedures, including splenectomy, tumor removal, prosthetic heart valve placement, surgical excision of the duodenum (where iron absorption occurs), partial or total gastrectomy (which removes parietal cells, thus reducing intrinsic factor needed for the absorption of cobalamin [vitamin B₁₂]), gastric bypass (where the duodenum may be bypassed and parietal cell surface area decreased), and ileal resection (where cobalamin absorption takes place). Also assess how wound healing progressed postoperatively and if and when any bleeding problems occurred in relation to the surgery. Discuss wound healing and bleeding as responses to past injuries (including minor trauma) and to dental extractions. Also determine the number of previous blood transfusions and possible complications during administration, since the risk of transfusion reactions and iron overload increases with the number of blood transfusions.