Diagnosing Syndrome‐Like Microangiopathic Hemolytic Anemia After Pit Viper Envenomation: Overcoming Laboratory Gaps in a Resource‐Limited Setting: A Case Report From Nepal

ABSTRACT

Snakebite envenomation remains a significant yet often overlooked health challenge in Nepal, particularly in its rural and hilly regions. While venom‐induced consumption coagulopathy (VICC) is commonly observed with viper bites, microangiopathic hemolytic anemia (MAHA) is an extremely rare complication, especially with green pit vipers (Trimeresurus spp.). MAHA is often underdiagnosed in low‐resource settings due to the absence of definitive laboratory diagnostics. We report a case of a 47‐year‐old woman from rural Nepal who was bitten by a presumed green pit viper (Trimeresurus spp.). She developed local swelling, ecchymosis, hematuria, anemia, thrombocytopenia, and coagulopathy. MAHA was diagnosed clinically based on syndromic presentation and serial hematologic monitoring, despite the unavailability of a peripheral blood smear. Due to species‐specific antivenom unavailability, the patient was treated with supportive care and blood product transfusions, and she achieved complete recovery without any renal complications. This case highlights the diagnostic challenges of MAHA in settings lacking definitive laboratory tests. It emphasizes the importance of clinical vigilance and syndromic diagnosis. Prompt, appropriate supportive management can lead to favorable outcomes even without antivenom availability. MAHA should be considered in snakebite victims presenting with thrombocytopenia and anemia. Strengthening diagnostic capacity and improving access to species‐specific antivenoms are critical for reducing morbidity and mortality from snakebite envenomation in resource‐limited settings.

Key Clinical Message

• MAHA is a rare but serious complication of green pit viper bites.

• Clinical vigilance and syndromic diagnosis are essential where laboratory tests and species‐specific antivenoms are unavailable.

• Early supportive treatment can lead to full recovery, underscoring the need to strengthen healthcare resources.

Abbreviations

AKI

acute kidney injury

APTT

activated prothrombin thromboplastin time

FEU

fibrinogen equivalent units

FFP

fresh frozen plasma

INR

international normalized ratio

LDH

lactate dehydrogenase

MAHA

microangiopathic hemolytic anemia

PBS

peripheral blood smear

PRBC

packed red blood cells

PT

prothrombin time

spp.

species

TMA

thrombotic microangiopathy

TPE

therapeutic plasma exchange

VICC

venom‐induced consumption coagulopathy

1. Introduction

Snakebite envenomation is a significant yet neglected public health issue in South Asia, particularly in Nepal. There are an estimated 20,000 to 37,000 incidents annually, which cause 1000 to 3200 deaths each year [1, 2]. The Terai region is predominantly inhabited by cobras (Naja spp.) and kraits (Bungarus spp.), while hill regions harbor pit vipers, mainly Trimeresurus spp. and Ovophis monticola [1, 3].

Venoms from the Viperidae family frequently result in systemic hematologic and renal complications such as venom‐induced consumption coagulopathy (VICC), shock, acute kidney injury (AKI), and bleeding disorders [4]. Microangiopathic hemolytic anemia (MAHA), a subset of thrombotic microangiopathy (TMA), involves mechanical fragmentation of erythrocytes in small vessels, often accompanied by thrombocytopenia and renal impairment [5, 6, 7]. Diagnosis depends on the detection of schistocytes in a peripheral blood smear (PBS), a test often unavailable in resource‐limited rural healthcare settings.

Although confirmed cases of thrombotic microangiopathy have not been reported in Trimeresurus spp., some evidence of VICC exists for this species [5]. Thrombotic Microangiopathy (TMA) is a broader pathological syndrome characterized by the triad of MAHA, thrombocytopenia, and organ injury caused by microvascular thrombosis [5].

We describe a case of presumed Trimeresurus spp. envenomation in a woman who developed MAHA‐like features. Despite lacking a confirmatory PBS and species‐specific antivenom, she was successfully managed with supportive care based on clinical evaluation and serial hematologic monitoring. This report highlights the challenges and importance of clinical vigilance in diagnosing and managing snakebite complications in resource‐limited settings, consistent with CARE Case Report guidelines [8].

2. Clinical Presentation

A 47‐year‐old woman, a farmer with no known comorbidities, presented to the emergency department approximately 6 h after sustaining a snakebite on the middle finger of her left hand while cleaning her home (Figure 1). According to the patient, the snake was green and approximately 50 cm in length, which is what a pit viper (Trimeresurus spp.) looks like in that area. Definitive species identification was not possible due to the absence of photographic evidence or specimen collection, and no herpetological consultation was available.

FIGURE 1.

Bite site from a presumed green pit viper (Trimeresurus spp.) on the left middle finger.

As explained by the patient, within 30 min of the bite, she experienced severe pain and rapidly progressive swelling localized to the bitten finger and hand. This was soon followed by the development of ecchymosis beneath both eyes (Figure 2A), suggesting early systemic envenomation. Over the subsequent hours, her condition worsened, with the onset of headache, diffuse chest and abdominal pain, two episodes of non‐projectile, non‐bilious vomiting, and visible hematuria. Minimal bleeding from the fang puncture site was noted and ceased spontaneously.

FIGURE 2.

(A–D) Ecchymosis under both eyes and on other body areas displaying systemic envenomation effects.

Upon arrival at the hospital, approximately 6 h post‐bite, her vital signs were stable (blood pressure 100/60 mmHg, heart rate 81 bpm, respiratory rate 22 breaths/min, and oxygen saturation 98% in room air). Physical examination revealed significant localized swelling extending proximally from the bite site up to the elbow, with ecchymosis visible over multiple sites, including periorbital regions (Figure 2A), arms (Figure 2B), and lower limbs (Figure 2C,D). Mild abdominal distension was present without tenderness or guarding. Neurological examination was unremarkable; no cranial nerve deficits, sensory abnormalities, or motor weakness were noted. Cardiovascular and respiratory examinations were normal.

2.1. Laboratory Findings

Initial laboratory evaluation revealed significant hematologic abnormalities summarized in Table 1. The hemoglobin level was markedly low, with progressive anemia evident on serial testing. Thrombocytopenia and prolonged prothrombin time with elevated international normalized ratio (INR) indicated consumption coagulopathy. Elevated lactate dehydrogenase (LDH) and D‐dimer suggested hemolysis and coagulation activation. Peripheral blood smear (PBS), essential for detecting schistocytes characteristic of microangiopathic hemolytic anemia (MAHA), was not performed due to a lack of supply.

TABLE 1.

Key laboratory trends over time during hospitalization.

Parameter	Day 1 (admission)	Day 2	Day 5	Reference range (adult female)
Hemoglobin (g/dL)	7.5↓	6.2↓	9.8↓	12–16
Platelet count (×109/L)	68↓	70↓	246	150–400
Prothrombin time (s)	21↑	17↑	24↑	≤ 13–14
INR	1.6↑	1.3	—	0.8–1.3
Serum creatinine (mg/dL)	0.93	—	—	0.5–1.1
WBC (×109/L)	8.4	—	—	4–11
LDH (U/L)	437.1↑	—	—	103–227
D‐dimer (mg/L FEU)	> 10↑	—	—	0–5
Total bilirubin (mg/dL)	1.2	—	—	0.2–1.2
Direct bilirubin (mg/dL)	0.13	—	—	0–0.4
Peripheral blood smear	Not performed*	Not performed*	—	—
Serum haptoglobin	Not performed*	Not performed*	—	—

Note: ↑ Elevated, ↓ Decreased; * Not performed due to lack of supply.

Based on the constellation of clinical signs and initial laboratory findings (Table 1), systemic envenomation was strongly suspected.

Abdominal ultrasonography conducted on day 2 of hospital admission revealed a medium‐sized abdominal hematoma with moderate peritoneal fluid collection with no active bleeding or rupture of adjacent organs. The patient maintained adequate respiratory function throughout hospitalization.

2.2. Management and Outcome

Due to the unavailability of species‐specific antivenom, supportive care was initiated. The patient received:

• 2 units of fresh frozen plasma

• 2 units of packed red blood cells

• Intravenous crystalloid fluids,

• Antipyretics, analgesics, and antiemetics

Despite an initial worsening anemia and coagulopathy, no acute renal injury occurred. Close clinical and laboratory monitoring allowed timely adjustments in supportive care.

By day 7, ecchymosis had resolved, hematuria ceased, and her vitals remained stable. She was discharged in stable condition with advice for outpatient follow‐up.

3. Discussion

Snakebite envenomation remains a major public health issue in South Asia, especially in rural regions where access to species‐specific antivenoms and advanced diagnostic tools is limited. In Nepal alone, snakebites contribute substantially to morbidity and mortality, underscoring the need for improved healthcare resources and training. Members of the Viperidae family, including green pit vipers, are well known for their hemotoxic venom, which often leads to venom‐induced consumption coagulopathy (VICC) by disrupting the coagulation cascade. In certain instances, this process may advance to thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, usually validated and confirmed by the detection of fragmented red blood cells (schistocytes) on a peripheral blood smear (PBS). Pathophysiology involves endothelial injury of the wall of a small vessel and microvascular thrombosis, leading to mechanical destruction of erythrocytes within the small vessel and resultant vaso‐occlusive ischemic end‐organ injury [5].

In this case, the patient exhibited characteristic signs of microangiopathic hemolytic anemia (MAHA), like deteriorating anemia, thrombocytopenia, and significant hematuria with extensive ecchymosis across the body. The lack of a peripheral smear in resource‐limited settings exemplifies the diagnostic challenges clinicians face in confirming MAHA. Even so, the combination of the clinical presentation and the serial laboratory trends gave strong syndromic evidence to support the diagnosis. In such contexts, reliance on clinical judgment and hematologic monitoring is crucial.

Comparable cases have been documented in the region. For instance, in Jajarkot, Nepal, a confirmed Cryptelytrops species (green pit viper) bite resulted in coagulopathy and local tissue swelling. The patient was effectively treated with only supportive care, despite the absence of antivenom [9]. Similarly, a paper by Pandey et al. exclusively outlined the management of Trimeresurus albolabris envenomation using clinical judgment and continuous laboratory monitoring in the absence of conclusive diagnostic testing [3]. These papers justify the importance of maintaining a high index of suspicion and utilizing syndromic diagnosis in low‐resource environments.

A broader regional perspective significantly demonstrates the potentially severe consequences of hemotoxic envenomation. As in Sri Lanka, Herath et al. documented multiple cases of Hypnale spp. (hump‐nosed viper) bites, which led to microangiopathic hemolytic anemia (MAHA) and acute kidney injury (AKI), which required dialysis for many patients [10]. In contrast, our patient did not develop AKI, potentially attributable to prompt intravenous fluid resuscitation and the quick identification of systemic envenomation, which likely had a protective function.

Joseph et al. undertook a study elucidating cases of Hypnale hypnale envenomation in southern India, which escalated to life‐threatening coagulopathy and severe renal failure in the absence of antivenom [11]. While therapeutic plasma exchange (TPE) has been explored as a potential treatment for snakebite‐associated thrombotic microangiopathy (TMA), current evidence remains inconclusive, and its applicability in resource‐limited settings is minimal [5, 12]. This example further demonstrates that timely supportive care, including blood product transfusions, intravenous fluids, and constant clinical monitoring, can lead to complete recovery, even in the absence of antivenom or sophisticated therapeutic measures.

4. Conclusion

This case report significantly underscores the urgent need to strengthen healthcare systems in rural and resource‐limited areas of Nepal and similar settings. To improve snakebite management, it is crucial to ensure that frontline healthcare professionals possess fundamental diagnostic tools, a consistent supply of effective species‐specific antivenoms, and ongoing training to recognize and manage the syndromic presentation of snakebite envenomation. Bridging these gaps can significantly reduce the incidence of illness or mortality associated with envenomation in resource‐limited settings.

Author Contributions

Prabhat Kaphle: conceptualization, data curation, formal analysis, funding acquisition, investigation, resources, software, supervision, validation, visualization, writing – original draft, writing – review and editing. Pukar Gupta: conceptualization, data curation, funding acquisition, investigation, software, supervision, validation, visualization, writing – original draft, writing – review and editing. Sarjan Shrestha: investigation, resources, writing – original draft, writing – review and editing. Neeru Diyali: resources, writing – original draft, writing – review and editing. Raj Kumar Koirala: writing – original draft, writing – review and editing. Amrita Shrestha: resources, writing – review and editing. Dhanlaxmi Giri: resources, writing – review and editing. Nabin Pahari: resources, writing – review and editing. Anil Kumar Sah: writing – original draft, writing – review and editing. Kamal Hamal: writing – original draft, writing – review and editing. Sujan Bohara: writing – original draft, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent form is available for review by the editor‐in‐chief of this journal upon request.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The datasets supporting the conclusions of this article are included within the article.