Thrombosis, embolism and DIC

Thrombosis is the formation of a blood clot (thrombus) inside a vessel in a living person. Three kinds of abnormality favor it, and most thrombi need more than one.

Flow speed decides composition. In arteries and the heart, fast flow sweeps red cells past, and the thrombus grows from platelets that stick to injured endothelium, held together by fibrin: a pale, gray-white thrombus, usually on a ruptured atherosclerotic plaque in coronary, cerebral or femoral arteries. In veins, slow flow lets the whole blood clot: a soft, dark red thrombus made mostly of red cells trapped in fibrin, with fewer platelets and white cells. Venous thrombi grow in the direction of flow, toward the heart, which is why their loose tails embolize.

A thrombus that formed in flowing blood is laminated: pale layers of platelets and fibrin alternate with darker layers of red cells. These lines of Zahn prove it formed during life. A postmortem clot forms in still blood after death: it is gelatinous, not attached to the wall, and settles into a dark red dependent part (“currant jelly”) under a yellow, plasma-rich upper part (“chicken fat”), with no laminations.

• Propagation: more platelets and fibrin are added and the thrombus grows until it occludes the vessel.
• Embolization: all or part breaks off and travels downstream.
• Dissolution: plasmin (fibrinolysis) removes it, mainly when it is recent; the basis of thrombolytic therapy, which works only in the first hours.
• Organization and recanalization: endothelial cells, smooth muscle cells and fibroblasts grow into an older thrombus; new channels form through it and partly restore flow, while the rest becomes a fibrous scar in the wall.

A thrombus can also become infected (septic thrombophlebitis, mycotic aneurysm). Which fate occurs depends on size, age and site; most deep vein thrombi either dissolve or organize, and the dangerous ones are those that embolize first.

Embolism is a detached mass (clot, fat, gas, amniotic fluid) carried by the blood to a distant site. More than 95% of pulmonary emboli come from deep veins of the legs above the knee (popliteal, femoral, iliac) and the pelvis. The thrombus breaks off, passes through the right heart and lodges where the pulmonary artery tree becomes too narrow. What follows depends on the size of the embolus and on the patient's circulation.

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Gas exchange changes in a recognizable way. Blood is diverted from the blocked arteries to the rest of the lung, creating low V/Q units and hypoxemia; hypoxemia, pain and receptor stimulation drive hyperventilation, so the classic gas is a low PaO₂ with a low PaCO₂ and respiratory alkalosis (Sim. Q32, worked in 4.4). The dead space itself wastes ventilation but is not what lowers PaO₂.

A systemic (arterial) embolus travels in arteries. Most come from thrombi in the left heart: a mural thrombus on an infarcted left ventricular wall, or a thrombus in a dilated left atrium in mitral stenosis or atrial fibrillation. Others come from atrial myxoma fragments, valve vegetations (sterile or infective), and ulcerated plaques or aneurysms of the aorta. They lodge in the lower limbs most often, then the brain, small bowel, spleen, kidneys and upper limbs, and the territory beyond them infarcts.

A paradoxical embolus starts in a vein but ends in an artery. It crosses from the right to the left side of the heart through a septal defect: most often a patent foramen ovale, or an atrial or ventricular septal defect. It needs right-sided pressure to exceed left, which happens transiently with coughing or straining and persistently after earlier pulmonary emboli. The clue is a systemic infarct (often a stroke) in a patient with a leg DVT.

Fat embolism follows fractures of long bones (femur) or the pelvis, and less often liposuction or fatty liver. Marrow fat globules enter torn marrow sinusoids and venules and lodge first in pulmonary capillaries; some pass through pulmonary arteriovenous shunts into the systemic circulation. The fat embolism syndrome appears 1–3 days after the injury in a minority of patients: dyspnea and tachypnea, confusion, delirium or coma, and petechiae over the chest, axillae and upper limbs, often with thrombocytopenia and anemia. The globules block vessels mechanically, and free fatty acids released from them injure endothelium.

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Amniotic fluid embolism occurs during labor or just after delivery through tears in placental membranes or uterine veins. Amniotic fluid in the maternal circulation causes sudden cardiorespiratory collapse (possibly an anaphylactoid reaction to fetal material) and DIC, because amniotic fluid is rich in procoagulants (tissue factor). Abrupt dyspnea, cyanosis, hypotension and bleeding follow; more than half die within an hour. At autopsy, fetal squamous cells, lanugo hair, vernix fat and mucin are found in the maternal pulmonary vessels.

Decompression sickness is a gas embolism. Breathing air at depth dissolves more nitrogen in blood and tissue; a rapid ascent lets it come out of solution as bubbles in tissues and vessels. Bubbles cause severe pain in joints, muscles and bones (“the bends”), pulmonary edema, hemorrhage and alveolar collapse (“the chokes”), and spinal cord ischemia mimicking cord trauma (back pain, loss of sphincter tone). Treatment is recompression in a hyperbaric chamber. Persistent bubbles in bone cause ischemic necrosis of the femoral and humeral heads (caisson disease).

In DIC, a trigger exposes the blood to tissue factor or damages endothelium everywhere at once. Thrombin forms throughout the microcirculation, and two opposite problems follow. Microthrombi block small vessels (ischemic injury of kidneys, lungs, brain, adrenals) and shear red cells into fragments (schistocytes: microangiopathic hemolytic anemia). Meanwhile platelets and clotting factors are consumed and fibrinolysis is activated, so the patient bleeds: oozing from venipuncture sites, mucosal and skin hemorrhages.