Blood Products in Bothropic Envenomation: Solution or Fuel? Understanding the Pathophysiology for Proper Management

fundacionvivarium
4 days ago
4 min read

In emergency clinical practice, medical intuition often follows a simple rule: if something is missing, replace it. When treating a patient bitten by a Bothrops species (mapanare, terciopelo, rabofrito, equis) who presents with profuse bleeding and low fibrinogen levels, the clinical instinct frequently leads to ordering fresh frozen plasma (FFP) or cryoprecipitate immediately.

However, in the acute phase of envenomation, this linear logic is not only incorrect—it is a serious clinical error that can cost the patient’s life.

In this article, we break down the pathophysiology behind Bothrops-induced coagulopathy and clarify when the use of blood products is a mistake, as well as the specific (and late) situations in which they become a necessary resource.

THE VICIOUS CYCLE: Why Blood Products Should Not Be Used in the Acute Phase

The venom of Bothrops snakes is a complex cocktail of enzymes, mainly metalloproteinases and serine proteases (thrombin-like enzymes). These toxins act by massively consuming coagulation factors, especially fibrinogen.

When a clinician administers plasma or cryoprecipitate while venom is still circulating actively in the bloodstream (that is, before it has been neutralized with antivenom), the following occurs:

Substrate loading: New coagulation factors are introduced — the “fuel.”

Enzymatic activation: The venom, acting as an insatiable enzyme, immediately attacks these newly supplied factors.

Generation of degradation products: The accelerated destruction of these factors produces more fibrin/fibrinogen degradation products, which themselves have anticoagulant properties.

Clinical worsening: The result is the “Vicious Cycle.” Laboratory values fall even further, bleeding worsens, and the clinician—alarmed—administers more blood products, perpetuating the damage.

SIGNS OF NEUTRALIZATION:The Green Light

Before even considering the blood bank, the priority must be full neutralization of the venom. Clinically, we know the venom has been neutralized when:

Active bleeding stops (gingival bleeding, hematuria, other hemorrhages).
Fibrinogen levels stop falling.
Coagulation times (PT/aPTT) begin to show a trend toward improvement.

Once the venom has been neutralized, the patient’s liver is usually able to restore coagulation factors within 24 to 48 hours without external assistance.

THE EXCEPTION TO THE RULE: When Blood Products Should Be Used

To avoid demonizing a therapeutic resource that is vital in the right context, we must turn to the specialized literature to understand the nuances. Not all situations occurring after 24 hours are managed the same.

Dr. César Rengifo, a Venezuelan clinical toxicologist, in his work “Serpientes, Venenos y Tratamiento Médico en Venezuela” (3rd Edition), makes a brilliant and necessary distinction between two phenomena that are often confused:

Libro de Serpiente Venenos y Tratamiento Cesar Rengifo

Recurrence of Envenomation (Requires Antivenom)

This occurs when signs of envenomation reappear (bleeding, edema, coagulopathy) after initial control—usually 24 hours or more later.

Cause:Delayed release of venom that had accumulated in the lymphatic system or deep subcutaneous tissue (common in bites from large snakes).

Management:The patient must be reassessed, and if laboratory abnormalities are present (falling fibrinogen, elevated CK/LDH), additional doses of antivenom—not blood products—must be administered.

Recurrence of Coagulopathy (May Require Blood Products)

This is the specific scenario in which the blood bank becomes relevant. It is characterized by a patient who, more than 24 hours after neutralization, presents with:

Normal fibrinogen
Elevated INR (prolonged clotting times)
No active bleeding

According to Dr. Rengifo:

“There are three factors to consider: 1) Incomplete neutralization of some minor venom components, such as L-amino oxidases…2) Idiosyncratic patient factors… 3) Association with leukocytosis and rhabdomyolysis.”

In these specific cases of Recurrence of Coagulopathy (distinct from the recurrence of active envenomation), Rengifo clarifies:

“Remember that in these cases, correction is usually not achieved with additional antivenom, but rather with blood products such as cryoprecipitate and fresh plasma, along with management of rhabdomyolysis and appropriate antibiotic therapy for leukocytosis.”

Conclusion

Evidence-based medicine requires us to abandon obsolete practices. In Bothrops envenomation:

Acute Phase: The treatment is antivenom. Using plasma before the venom has been fully neutralized is counterproductive.

Late Phase (Venom Recurrence): If bleeding returns and fibrinogen drops, more antivenom is needed.

Late Phase (Residual Coagulopathy): If fibrinogen is normal but the INR remains elevated without bleeding, this is where blood products and clinical support have their place.

Education saves lives. By understanding the pathophysiology, we avoid turning a solution into part of the problem.

References:

Rengifo, C. et al. (2024). Serpientes, Venenos y Tratamiento Médico en Venezuela (3rd Edition). EBUC-UCV.
World Health Organization (WHO). (2016). Guidelines for the Management of Snakebites. Regional Office for South-East Asia. (States that coagulation factors should only be used if severe bleeding persists after venom neutralization.)
Pan American Health Organization (PAHO). Guidelines for the Clinical Management of Snakebite Envenomation in Latin America and the Caribbean. (Emphasizes the central role of specific antivenom therapy.)
White, J. (2005). Snake venoms and coagulopathy. Toxicon, 45(8), 951–967. (Detailed description of Venom-Induced Consumption Coagulopathy — VICC.)

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