Hematological manifestations of systemic disease

1

Describe the systemic diseases that have hematological manifestations.

Almost all systemic conditions can result in some degree of derangement of the hematological system. Conditions associated with inflammation can cause increase in platelets, which are an acute phase reactant, as well as anemia, typically because of impaired iron metabolism. Other disruptions in nutrients critical to hematologic system can also cause derangements. In other cases, particular organ dysfunction, such as liver and kidney disease, can disrupt production and regulation of blood cells and factors. Lastly, some conditions can result in impairment of blood cell function. For these reasons, hematological manifestations of disease can be seen with cardiac, pulmonary endocrine, gastrointestinal, rheumatological, metabolic, nervous system, renal, and liver conditions.

2

What hematological disorders are seen in cardiac disease?

• Polycythemia is a well-known consequence of cyanotic heart disease as a compensatory mechanism to increase oxygen-carrying capacity.

• Coagulation abnormalities appear to be associated with the degree of polycythemia. The exact cause is not clear; however, it has been postulated that the tissue hypoxia that results from the hyperviscosity may cause a consumptive process.

• Thrombocytopenia is also related to cyanotic heart disease. The degree of thrombocytopenia correlates with the severity of the polycythemia and with ongoing hypoxia. Platelet production in the bone marrow has been demonstrated to be normal; however, platelet survival is diminished. These patients may additionally have platelet aggregation defects.

• Individuals who have prosthetic heart valves generally have some hemolysis of red blood cells (RBCs) because of direct mechanical injury. The degree of hemolysis may or may not be severe enough to cause anemia.

3

Discuss the hematological disorders seen in renal disease.

• Renal disease is most commonly associated with anemia. This anemia is classified as normocytic, normochromic anemia. The anemia is caused by a deficiency of erythropoietin, which is primarily produced in the kidney. RBC survival also may be decreased because of uremia when renal disease is severe.

• Uremia also has an effect on the clotting factor levels, specifically factors V, VII, IX, and X. In addition, patients with renal protein losses may be prothrombotic because of losses of protein C and S.

• Platelet survival and platelet function also may be diminished in renal disease.

• Patients on dialysis often become deficient in folic acid and can have transient sequestration of granulocytes, resulting in granulocytopenia.

• In terms of management, patients demonstrating anemia should be on erythropoietin replacement, plus daily folate and iron supplementation.

4

What hematological disorders are seen in liver disease?

• Liver disease has most commonly been associated with coagulation abnormalities. The liver is involved in the synthesis of many of the clotting factors; therefore when there is liver dysfunction, factor levels are diminished. The vitamin K–dependent factors are the factors that are most affected: factors II, VII, IX, and X. Factor VII is the most severely and acutely affected factor because its synthesis takes place almost entirely in the liver and it has a very short-half life. Factor VIII is generally unaffected in liver disease or is elevated because it is produced by the endothelium and is an acute phase reactant. For these reasons, the prothrombin time (PT) may be prolonged before the activated partial prothrombin time (PTT) in patients with early liver disease. When the liver damage is caused by obstruction, fibrinogen may be elevated, as may factors XI and XII and antithrombin III. Additionally, proteins C and S are also low in patients with liver disease. Therefore patients with liver disease have a “balanced” coagulopathy that is prone to both bleeding and clotting.

• Anemia associated with liver disease is multifactorial. It is typically macrocytic, which is because of folate deficiency. There is also decreased RBC survival, which is probably because of dysfunction of the antioxidant system. Patients who develop portal hypertension may develop hypersplenism and subsequent splenic sequestration. Additionally, patients may have varices, which are prone to bleeding, leading to the development of iron-deficiency anemia.

• If patients are folate deficient or iron deficient, they should be on daily supplementation. Vitamin K supplementation may help transiently correct the coagulation defects.