Viral Hemorrhagic Fever: What It Is and Why Ebola Causes Bleeding

What Is Viral Hemorrhagic Fever?

Viral hemorrhagic fever (VHF) is not a single disease — it’s a clinical syndrome that describes a severe illness caused by several distinct virus families, all sharing common features:

1. Fever — high, often sudden onset
2. Hemorrhage (bleeding) — from multiple sites, due to disrupted clotting and vascular damage
3. Multi-organ involvement — affecting multiple body systems
4. High case fatality rates — ranging from ~5% (some arenaviruses) to 90% (Ebola Zaire strain)

The term “hemorrhagic” is somewhat misleading: while bleeding is characteristic, it is not always the primary cause of death and is absent in some patients. The critical pathological feature is vascular dysfunction — the breakdown of the blood vessel wall’s integrity — leading to fluid leakage, shock, and multi-organ failure.

What Viruses Cause VHF?

VHF is caused by four distinct virus families, all of which are RNA viruses with specific geographic distributions and transmission routes:

1. Filoviridae (Thread Viruses)

The most famous VHF family. Named for their thread-like appearance under electron microscopy.

• Ebolaviruses: Five species (Zaire, Sudan, Bundibugyo, Tai Forest, Reston) — covered in detail throughout this site
• Marburg virus: Closely related to Ebola, similar disease, CFR up to 88%

Geographic range: Sub-Saharan Africa, with Reston ebolavirus in Asia Reservoir: Fruit bats

2. Arenaviridae (Sand Viruses)

Two subdivisions: Old World and New World arenaviruses.

• Lassa fever (Old World): West Africa (Sierra Leone, Nigeria, Guinea). 300,000–500,000 estimated annual cases, 5,000 deaths. Spreads via rodents (Mastomys natalensis).
• Lymphocytic choriomeningitis virus (LCMV) (Old World): Mild VHF in humans, mainly from house mice
• Junin, Machupo, Guanarito, Sabia (New World, South America): Limited geographic distribution, rodent-borne

3. Bunyaviridae (Now reclassified into multiple families)

• Crimean-Congo Hemorrhagic Fever (CCHF): Tick-borne; Africa, Middle East, Eastern Europe, Central Asia. CFR 10–40%.
• Hantavirus Pulmonary Syndrome (HPS): Americas; rodent-borne. Primarily lung disease with hemorrhagic features.
• Rift Valley Fever (RVF): Sub-Saharan Africa, Arabian Peninsula; mosquito and direct animal contact.

4. Flaviviridae

• Yellow fever: Africa and South America; mosquito-borne. Preventable by vaccine.
• Dengue hemorrhagic fever: Tropical regions worldwide; mosquito-borne. Dengue fever can progress to DHF in some cases.

The Biology of Hemorrhage in VHF

Why do these different viruses all cause bleeding? The answer lies in their shared ability to damage the vascular endothelium (the inner lining of blood vessels) and disrupt the coagulation cascade.

Endothelial Injury

Blood vessels are lined by a single layer of endothelial cells. This layer is critical for:

• Maintaining the barrier between blood and tissues
• Regulating clotting (by secreting anticoagulants and procoagulants in balance)
• Controlling vascular tone

VHF viruses — particularly filoviruses — either infect endothelial cells directly or damage them indirectly through inflammatory mediators (cytokines). When endothelial cells are damaged:

• Vascular permeability increases: fluid leaks from blood into tissues (causing oedema and reducing circulating blood volume)
• The coagulation balance shifts toward pro-coagulant state

Disseminated Intravascular Coagulation (DIC)

In severe VHF, the combination of endothelial injury, inflammatory cytokines, and viral proteins triggers DIC — the simultaneous activation of clotting pathways throughout the entire vascular system.

In DIC:

1. Widespread micro-clots form in small blood vessels (thrombosis)
2. Clotting factors and platelets are consumed faster than the liver can replace them
3. Once clotting factors are depleted, the blood cannot clot at all
4. Result: both bleeding (hemorrhage) AND clotting (ischemia) occur simultaneously

This paradoxical state explains why VHF patients bleed from IV puncture sites, mucous membranes, and the GI tract — and also why they can simultaneously develop ischemic organ damage.

Thrombocytopenia (Low Platelets)

VHF viruses commonly cause significant drops in platelet count. Platelets are essential for initial clot formation (primary hemostasis). When platelet counts fall below critical thresholds, even minor trauma can cause prolonged bleeding.

How Ebola Specifically Causes Bleeding

For Ebola specifically, the hemorrhagic features develop through a multi-stage process:

1. Macrophage and dendritic cell infection: Ebola infects immune cells first, spreading systemically
2. Cytokine storm: Infected macrophages release massive quantities of TNF-α, IL-6, IL-1β — triggering systemic inflammation
3. Endothelial activation: Cytokines activate endothelial cells, increasing vascular permeability
4. Direct endothelial infection: By late disease, endothelial cells themselves are infected
5. DIC: Coagulation cascade activated throughout vascular system
6. Liver failure: Liver dysfunction reduces synthesis of clotting factors (VII, X, fibrinogen, prothrombin)
7. Adrenal failure: Cortisol deficiency contributes to vascular tone loss and refractory hypotension

The hemorrhagic manifestations — bleeding from the gums, nose, eyes, and IV sites — typically appear in week 2 of illness, in severe cases. They are a sign of advanced, severe EVD, not an early symptom.

Common Misconceptions

Misconception 1: “Ebola makes you bleed out of every orifice”
Reality: Dramatic hemorrhage is a late feature seen in a minority of patients (approximately 20–50%). Most Ebola deaths are from hypovolemic shock and multi-organ failure, not exsanguination.

Misconception 2: “Viral hemorrhagic fevers are all the same”
Reality: Lassa fever (relatively mild, treatable with ribavirin), dengue hemorrhagic fever (millions of cases annually, <1% CFR with good care), and Ebola (CFR 60–90% untreated) are vastly different in severity and epidemiology.

Misconception 3: “VHF always causes fever AND bleeding”
Reality: Some patients with VHF infections never develop significant hemorrhage. The clinical spectrum ranges from mild febrile illness to fulminant hemorrhagic shock.

Treatment Principles Across VHF

While no single treatment works for all VHF, some general principles apply:

• Aggressive fluid resuscitation (with electrolyte monitoring) helps counteract hypovolemia
• Ribavirin is effective for Lassa fever and CCHF; not for Ebola or Marburg
• Monoclonal antibodies (Inmazeb, Ebanga) for Zaire ebolavirus specifically
• Platelet transfusion: sometimes used but evidence limited
• Avoid NSAIDs (aspirin, ibuprofen): these further impair platelet function
• Avoid unnecessary injections: minimise puncture wounds that may bleed