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Fibrin Clot Formation Abnormalities

When a wound occurs, several changes take place to minimize blood loss. First, the blood vessel slows
the flow of blood past the wound site. Next, platelets collect at the wound site to form a plug. Finally,
fibrin clots form scabs to replace these temporary platelet plugs. Fibrin clot formation is dependent on
adequate function of clotting factors. Multiple factors can prevent fibrin clot formation.

Coagulation Factor Abnormalities

Hepatocellular Disease. In patients with severe liver disease, such as hepatocellular carcinomas and
adenomas, insufficient clotting factors may be available to control bleeding. Treatment involves
transfusion and antifibrolytic medications such as e-aminocaproic acid (Amicar) and tranexamic acid.
Please see Liver Cancer.

Medications. Medications that can affect clot formation include heparin and warfarin (Coumadin).
Although both heparin and warfarin are used to prevent thrombosis (the formation of blood clots in the
blood vessels), bleeding is an uncommon but possible side effect. Risk factors for heparin-induced
bleeding include recent surgery, cardiopulmonary resuscitation (CPR), intracranial hemorrhage, stroke;
active peptic ulcer disease; high blood pressure; history of bleeding diathesis; elevated serum creatinine
(a blood protein); and age (women > 60, men > 70). Risk factors for warfarin-induced bleeding include
use of multiple drugs and coexisting serious illness such as kidney failure or congestive heart failure.
When severe heparin-induced bleeding occurs, protamine sulfate may be used to counteract the
bleeding tendency. Similarly in the presence of warfarin therapy, bleeding may be treated with vitamin K
supplements or transfusions.

Fibrinolytic Therapy. Fibrinolytic, or thrombolytic, agents are used to break up clots. The risk for
fibrinolytic-induced bleeding is much higher than it is for heparin or warfarin (Coumadin). Bleeding
depends on the dose, length of therapy, and the individual patient. The most serious bleeding threat is
intracranial hemorrhage (bleeding within the skull), a rare but usually fatal complication. Bleeding
requires immediate treatment, often with cryoprecipitate, platelets, or antifibrinolytic drugs.

Disseminated Intravascular Coagulation

In disseminated intravascular coagulation (DIC), both bleeding and clotting occur at the same time. DIC
occurs often in cancer patients (it is especially common with prostate cancer). DIC can result from burns,
surgery, cancer, injury, or toxins or foreign substances in the blood (such as bacteria). Hematological
symptoms arise due to bleeding or clotting in the specific organ affected. These include difficulty
breathing, unconsciousness and confusion, swelling in the limbs, bruising, petechiae, purpura, blood in
the urine and stool, and bleeding of wounds. The disorder is diagnosed based on patient history,
physical examination, and laboratory testing. Although it often exists as a low-grade problem, it can
quickly result in death. If bleeding or clotting become serious, they must be immediately treated with
blood transfusions and antifibrolytic medications such as heparin or e-aminocaproic acid (Amicar). If
possible, the underlying disease should be treated aggressively.
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Massive Blood Transfusion

When several blood transfusions have been administered, the fibrin in the blood may become too
dilute. Bleeding occurs because there is not enough fibrin for the amount of blood in the body. Platelet
transfusions may be used to improve clotting function. Another cause of bleeding following red cell
transfusion is elevated levels of citrate anticoagulant. Accumulation of citrate anticoagulant, which is
added to transfused blood, decreases fibrin’s clotting ability. In patients at risk, blood with low levels of
citrate is used for transfusion.

Snake and Spider Bites

Some snake and insect bites contain toxins that produce bleeding by interfering with fibrin’s activity. For
instance, bleeding may result from bites from the eastern and western diamondback rattlesnakes, the
saw-scaled viper, the viperine, the Russell viper, a species of caterpillar found in Venezuela and Brazil
(Lonoma achelous), and the brown recluse spider. These venoms often produce symptoms of
disseminated intravascular coagulation(DIC) and should be treated with antivenin and transfusion if
necessary.