Can Anaplasmosis Become Severe? Multiorgan Complications Explained

12% of hospitalized patients in a 2026 study required ICU-level care
Confusion, low platelets, elevated liver enzymes, and other abnormalities can accompany severe illness
Anaplasmosis may initially be mistaken for pneumonia, sepsis, or another infection

Can anaplasmosis become severe? Yes. Although many infections are relatively mild, anaplasmosis can occasionally cause serious or life-threatening illness involving the lungs, kidneys, liver, heart, nervous system, blood, and other organs.

A 2026 multicenter study provides new insight into critically ill patients with human granulocytic anaplasmosis. Researchers studied 101 adults hospitalized with PCR-confirmed Anaplasma phagocytophilum infection at Mayo Clinic sites in Minnesota and Wisconsin. Twelve patients, or 12%, required ICU-level care.¹

Patients requiring intensive care more often had gastrointestinal symptoms and certain laboratory abnormalities. They had lower sodium levels, higher bilirubin, lower platelet nadirs, and, among the small number tested, markedly higher ferritin levels.¹

Another published case illustrates why recognizing anaplasmosis can be difficult. An 81-year-old woman developed fever, fatigue, headache, muscle and joint pain, gastrointestinal symptoms, and confusion after spending time at a cabin in Pennsylvania. When she became ill in Ohio, she was initially treated for presumed community-acquired pneumonia before leukopenia, severe thrombocytopenia, and elevated liver enzymes prompted evaluation for a tick-borne infection.⁴

Importantly, these findings should not be interpreted as individual predictors of who will become critically ill. Severe anaplasmosis varies considerably between patients, and laboratory abnormalities must be interpreted in the context of the entire clinical picture.

How Often Did Hospitalized Patients Require Intensive Care?

Dumic and colleagues examined adults hospitalized between 2014 and 2024 at Mayo Clinic Rochester and affiliated Mayo Clinic Health System hospitals in Minnesota and Wisconsin.¹

All 101 patients had infection confirmed by whole-blood PCR, strengthening the diagnostic certainty of the study.

Among these hospitalized patients:

• 12% required ICU-level care.
• Approximately 24% experienced the study’s composite endpoint of an anaplasmosis-related complication or serious treatment-related adverse event.
• Among ICU patients, 75% met that composite endpoint compared with 17% of patients treated on general medical wards.
• One patient died, producing an overall mortality of approximately 1% in this hospitalized cohort.

The composite endpoint requires some caution. It included complications caused by severe anaplasmosis as well as rare serious treatment-related adverse events, including suspected antibiotic-associated anaphylaxis.

These percentages also apply specifically to hospitalized adults in this study. They should not be interpreted as the risk of ICU admission or death among everyone who develops anaplasmosis.

What Findings Were Associated With ICU-Level Anaplasmosis?

Several symptoms and laboratory findings differed between patients requiring ICU care and those managed on general medical wards.¹

Vomiting was reported in 64% of ICU patients compared with 30% of ward patients. Abdominal pain was also more common, occurring in approximately 55% of ICU patients compared with 26% of ward patients.

Several laboratory findings also differed:

• Sodium: mean 128.8 mmol/L in ICU patients vs. 132.3 mmol/L in non-ICU patients
• Total bilirubin: mean 1.3 mg/dL vs. 0.8 mg/dL
• Platelet nadir: mean 54.8 × 10⁹/L vs. 84.1 × 10⁹/L
• Acute kidney injury: 41.7% vs. 16.9%

These differences may help characterize the systemic illness seen in severe anaplasmosis, but they should not be used by themselves to determine whether an individual patient needs intensive care.

Some of the differences, including platelet nadir, acute kidney injury, and abdominal pain, did not meet the study’s conventional threshold for statistical significance. The investigators also emphasized that their analysis was exploratory and that there was substantial overlap between the ICU and non-ICU groups.¹

Extremely High Ferritin Was Seen in Some Critically Ill Patients

One of the most striking findings involved ferritin, an inflammatory marker that can become markedly elevated during severe infection and hyperinflammatory syndromes.

Among the limited number of patients in whom ferritin was measured, the median peak ferritin was 21,666 µg/L in ICU patients compared with 961 µg/L in non-ICU patients.¹

However, ferritin was available for only 13 patients—4 ICU patients and 9 non-ICU patients. It may also have been ordered preferentially in patients who appeared particularly ill. The finding therefore requires considerable caution and should be considered hypothesis-generating.

The authors raised another important consideration: very high ferritin can occur with secondary hemophagocytic lymphohistiocytosis (HLH), a rare hyperinflammatory syndrome that has been reported with anaplasmosis. One ICU patient in this study was diagnosed with HLH.¹

Markedly elevated or rising ferritin in a severely ill patient may therefore prompt clinicians to consider secondary HLH and other causes of hyperinflammation.

What Complications Occurred in ICU Patients?

Severe anaplasmosis can affect several organ systems simultaneously. Among the 12 ICU patients in the 2026 study, reported complications included:¹

• Shock
• Acute kidney injury
• Acute hypoxemic respiratory failure
• Myocarditis
• Hemophagocytic lymphohistiocytosis (HLH)
• Disseminated intravascular coagulation
• Rhabdomyolysis

Several patients experienced more than one complication.

Two ICU patients also developed suspected anaphylactic shock after empiric antibiotics were started—one after doxycycline and one after ceftriaxone. The researchers classified these as treatment-related adverse events rather than direct complications of anaplasmosis.¹

One patient died. This patient was immunosuppressed because of chemotherapy and developed a pulmonary embolism, severe iliopsoas myositis with rhabdomyolysis, and acute kidney injury requiring continuous renal replacement therapy. Initial empiric antibiotics did not include doxycycline, which was added after the diagnosis of anaplasmosis was established.¹

The cause of death was multifactorial, so this individual case cannot establish that delayed doxycycline alone caused the poor outcome.

Can Anaplasmosis Be Mistaken for Pneumonia or Sepsis?

Yes. Because early anaplasmosis can produce fever, weakness, headache, gastrointestinal symptoms, abnormal laboratory findings, and systemic illness, the initial presentation may resemble pneumonia, sepsis, a viral infection, or another acute illness.

Abraham and colleagues described an 81-year-old woman who was hospitalized in Cincinnati, Ohio, with fever and confusion after spending a week at a cabin in Emlenton, Pennsylvania.⁴

Her symptoms had begun four days earlier and included fever, fatigue, headache, muscle aches, diffuse joint pain, vomiting, and diarrhea. She had recorded a temperature of 104.1°F before presentation. She did not recall a tick bite.

At the hospital, she was somnolent and oriented only to herself. Diminished breath sounds and left-sided rales contributed to concern for a respiratory infection.

She was initially treated with ceftriaxone and azithromycin for presumed community-acquired pneumonia. However, imaging did not identify a clear pneumonia, and laboratory abnormalities pointed toward another explanation.⁴

Low Platelets, Low White Blood Cells, and Elevated Liver Enzymes Were Important Clues

The patient’s initial laboratory findings included:

• White blood cell count: 3.3 K/µL
• Platelet count: 29 K/µL
• ALT: 126 U/L
• AST: 214 U/L
• Creatinine: 1.7 mg/dL
• Sodium: 130 mmol/L

Her platelet count subsequently fell to a nadir of 15 K/µL, prompting platelet transfusion.⁴

The combination of leukopenia, thrombocytopenia, elevated liver enzymes, and compatible exposure history led the infectious-disease team to consider a tick-borne illness and start doxycycline.

This laboratory pattern is particularly important because leukopenia, thrombocytopenia, and elevated liver enzymes are commonly reported with anaplasmosis and may provide an early clue when the symptoms themselves are nonspecific.^5,6

A Negative Blood Smear Did Not Rule Out Anaplasmosis

The patient’s peripheral blood smear did not show morulae, the intracellular clusters that can sometimes be seen in neutrophils during anaplasmosis.⁴

Nevertheless, she improved after doxycycline was started, and PCR testing subsequently confirmed Anaplasma phagocytophilum infection.

This illustrates an important diagnostic point: the absence of visible morulae on a peripheral smear does not exclude anaplasmosis. Nucleic acid amplification testing such as PCR is generally more useful for establishing the diagnosis during acute infection.⁶

Travel History Can Matter Even When Anaplasmosis Is Uncommon Where a Patient Presents

The 81-year-old patient became ill in Ohio, where clinicians initially considered more common causes of her presentation. However, she had recently spent time outdoors in Pennsylvania.

The case illustrates why the location where a patient becomes sick is not necessarily the location where the infection was acquired.

Exposure history may therefore include:

• Recent travel
• Time spent at a cabin or vacation property
• Gardening or yard work
• Hiking or walking in wooded or grassy areas
• Outdoor recreation
• Exposure to ticks without a remembered tick attachment

A patient does not need to remember a tick bite for anaplasmosis to be considered. In a Pennsylvania cohort discussed by Abraham and colleagues, only 39% of patients recalled a tick bite, while approximately 80% reported outdoor activity.⁴

Can Anaplasmosis Become Life-Threatening?

Yes. Although most patients do not develop critical illness, severe anaplasmosis can cause respiratory failure, shock, kidney injury, bleeding abnormalities, severe inflammatory complications, and multiorgan dysfunction.^1,5

Reported complications of severe anaplasmosis include:

• Acute respiratory distress syndrome
• Respiratory failure
• Septic shock-like illness
• Kidney injury or kidney failure
• Liver dysfunction
• Bleeding disorders, including disseminated intravascular coagulation
• Rhabdomyolysis
• Myocardial dysfunction or myocarditis
• Neurologic complications
• HLH
• Multiorgan failure

Death remains uncommon but is possible, particularly with severe illness or when effective treatment is delayed.^5,6

Who Is at Greater Risk for Severe Anaplasmosis?

Previous studies have associated severe illness with older age, immunosuppression, underlying medical conditions, and delayed treatment.^5,6

Clinical circumstances associated with concern for severe disease may include:

• Older age
• Immune-suppressing medications
• Cancer treatment
• Organ transplantation
• Significant chronic medical conditions
• Delayed initiation of effective treatment

The average age of the hospitalized patients in the 2026 Mayo study was approximately 70 years. However, age did not differ significantly between ICU and non-ICU patients within this already hospitalized population.¹

Similarly, 92% of ICU patients had at least one comorbidity compared with 70% of non-ICU patients, but this difference was not statistically significant. The small number of ICU patients limited the study’s ability to identify independent risk factors.¹

What About Lyme Disease and Other Tick-Borne Coinfections?

Because the blacklegged tick can transmit multiple pathogens, patients with anaplasmosis may also have another tick-borne infection.

In the 2026 study, 14 of 101 hospitalized patients had a documented tick-borne coinfection. Nine had Lyme disease alone, two had Ehrlichia muris eauclairensis infection alone, two had both Lyme disease and E. muris eauclairensis, and one had Babesia microti infection.¹

Coinfection was documented in 33% of ICU patients compared with 11% of non-ICU patients. However, this difference did not reach statistical significance, and the number of coinfected ICU patients was very small. The study therefore does not establish that coinfection increases the risk of ICU admission.

In the Abraham case, Lyme serology showed positive IgG with negative IgM, which the authors interpreted as evidence of prior Lyme infection rather than the explanation for the patient’s acute illness.⁴

Clinicians may nevertheless need to consider tick-borne coinfections when a patient has an unusually severe presentation or does not improve as expected.

Confusion and Lethargy Were Early Warning Signs in Another Severe Case

An earlier case report illustrates how rapidly severe anaplasmosis can progress in an immunosuppressed patient.

Aydin and colleagues described a 66-year-old woman from Connecticut who was admitted with confusion and lethargy. She had experienced fever, chills, generalized weakness, and poor appetite for two days.²

Her medical history included rheumatoid arthritis, for which she was receiving methotrexate and upadacitinib. She enjoyed gardening and had discovered several ticks shortly before becoming ill. She did not have a noticeable rash.²

The absence of a rash did not exclude anaplasmosis. Rash is uncommon with anaplasmosis and, when present, may raise concern for another tick-borne infection or coinfection.

Laboratory Findings Suggested Severe Systemic Illness

Laboratory testing in the Aydin case revealed pancytopenia, hyponatremia, elevated liver enzymes, mild hyperbilirubinemia, and lactic acidosis.²

More commonly, patients with anaplasmosis develop leukopenia, thrombocytopenia, and elevated liver enzymes. In severe cases, additional abnormalities may reflect injury to the kidneys, liver, muscles, lungs, or other organs.⁵

PCR testing can be particularly useful during the early stage of illness, when antibody testing may still be negative.⁶

When anaplasmosis is strongly suspected, treatment generally should not be postponed solely while awaiting confirmatory testing because timely therapy is important during the acute phase of illness.^5,6

Respiratory Failure Can Occur

The woman in the Aydin case was treated promptly with doxycycline. Nevertheless, her condition initially worsened and she developed acute hypoxic respiratory failure secondary to acute respiratory distress syndrome.²

She required high-flow nasal cannula oxygen therapy but ultimately recovered with doxycycline and supportive hospital care.

Lung injury in severe anaplasmosis may result partly from the host inflammatory response rather than simply reflecting extensive direct infection of lung tissue.³

Why Can Anaplasmosis Affect Multiple Organs?

Anaplasma phagocytophilum infects neutrophils, white blood cells involved in the immune response. The organism interferes with normal neutrophil function while also influencing inflammatory signaling.

The severity of illness may therefore depend not only on the organism but also on the host immune response. Experimental and clinical evidence suggests that inflammatory and immunopathologic processes contribute to tissue injury in severe anaplasmosis.³

This may help explain why severe disease can involve blood counts, the liver, lungs, kidneys, nervous system, cardiovascular system, and other organs without requiring large numbers of organisms within each affected tissue.

HLH represents an extreme example of immune dysregulation. It can produce persistent fever, cytopenias, liver abnormalities, markedly elevated ferritin, and progressive organ dysfunction.

Early Treatment Remains Critical

Doxycycline is the standard first-line treatment for human granulocytic anaplasmosis.⁵

Because severe complications can develop quickly and laboratory confirmation may not be immediately available, treatment is generally started when the clinical presentation and exposure history strongly suggest anaplasmosis rather than waiting for every test result.^5,6

In the 2026 Mayo cohort, approximately 92% of both ICU and non-ICU patients received appropriate empiric therapy. Overall outcomes were favorable: 100 of the 101 hospitalized patients improved.¹

All but one patient were ultimately treated with doxycycline. The patient who developed suspected doxycycline-associated anaphylaxis was treated with rifampin.¹ This isolated circumstance should not be interpreted as evidence that rifampin is generally equivalent to doxycycline for treating anaplasmosis.

The Abraham case provides another example of why clinical recognition matters. Once the unusual combination of confusion, leukopenia, thrombocytopenia, elevated liver enzymes, and travel exposure prompted consideration of a tick-borne infection, doxycycline was started before PCR confirmation became available.⁴

The broader lesson is that symptoms, laboratory findings, geography, and exposure history need to be interpreted together.

Frequently Asked Questions

Can anaplasmosis become life-threatening?

Yes. A minority of patients develop severe complications such as respiratory failure, shock, kidney injury, bleeding abnormalities, HLH, or multiorgan failure. Death is uncommon but possible.

How often does anaplasmosis require ICU care?

In a 2026 study of 101 adults hospitalized with PCR-confirmed anaplasmosis, 12% required ICU-level care. This percentage applies to hospitalized patients in that study and should not be interpreted as the ICU risk for everyone who develops anaplasmosis.

What laboratory findings may occur with severe anaplasmosis?

Thrombocytopenia, leukopenia, elevated liver enzymes, hyponatremia, kidney injury, and other abnormalities may occur. In the 2026 study, ICU patients had lower sodium, higher bilirubin, lower platelet nadirs, and markedly higher ferritin among the small subset tested. These findings cannot individually predict whether a patient will require intensive care.

Can anaplasmosis cause very high ferritin?

Yes. Marked hyperferritinemia has been reported in severe anaplasmosis and may raise concern for an intense inflammatory response or secondary HLH. In the 2026 study, ferritin was measured in only a small subset of patients, so the finding should be interpreted cautiously.

Can anaplasmosis affect the kidneys?

Yes. Acute kidney injury can occur with severe anaplasmosis. In the 2026 hospitalized cohort, acute kidney injury was more frequent among ICU patients than among patients treated on general medical wards, although the difference did not reach statistical significance.

Can anaplasmosis cause confusion?

Yes. Confusion, disorientation, lethargy, and encephalopathy can occur, particularly during severe illness. Neurologic symptoms may reflect neurologic involvement, systemic infection, inflammation, metabolic abnormalities, organ dysfunction, or a combination of factors.

Can anaplasmosis be mistaken for pneumonia?

Yes. Early symptoms can be nonspecific. In a 2024 case report, an 81-year-old woman with fever and confusion was initially treated for presumed community-acquired pneumonia before leukopenia, thrombocytopenia, elevated liver enzymes, and her exposure history led clinicians to consider anaplasmosis. PCR subsequently confirmed the infection.

Does a negative blood smear rule out anaplasmosis?

No. Morulae may sometimes be visible within neutrophils, but their absence does not exclude infection. In the 2024 case, the peripheral blood smear did not show morulae, yet PCR subsequently confirmed Anaplasma phagocytophilum.

Do patients with anaplasmosis always remember a tick bite?

No. Many patients do not recall a tick attachment. Outdoor activity, travel, geography, symptoms, and laboratory findings may therefore be important even when no tick bite is remembered.

Should treatment wait for anaplasmosis test results?

Generally, no. When anaplasmosis is strongly suspected, doxycycline is typically started promptly while laboratory confirmation is pending because delayed effective treatment may increase the risk of severe illness.

Clinical Takeaway

Anaplasmosis often begins with nonspecific symptoms such as fever, fatigue, headache, muscle aches, chills, and gastrointestinal symptoms. Most infections do not progress to critical illness.

However, severe disease remains clinically important. In the 2026 Mayo study, 12 of 101 hospitalized adults with PCR-confirmed anaplasmosis required ICU-level care. Gastrointestinal symptoms, hyponatremia, hyperbilirubinemia, lower platelet counts, kidney injury, and marked hyperferritinemia were seen more prominently among critically ill patients, although none should be considered a stand-alone predictor of deterioration.¹

The 2024 Abraham case adds another practical lesson. An older patient with fever and confusion was initially treated for presumed pneumonia after becoming ill outside the state where she had likely been exposed. Leukopenia, severe thrombocytopenia, elevated liver enzymes, and the travel history ultimately raised suspicion for anaplasmosis. Her peripheral smear was negative for morulae, but PCR confirmed the infection.⁴

Anaplasmosis should therefore remain in the differential when a patient with compatible exposure develops an unexplained febrile systemic illness accompanied by low platelets, low white blood cells, elevated liver enzymes, confusion, or organ dysfunction—even when no tick bite is remembered and even when the patient becomes ill outside the area where exposure occurred.

This article is for educational purposes and is not a substitute for medical evaluation, diagnosis, or treatment. Patients with severe or rapidly worsening symptoms should seek prompt medical care.

Related Articles

Can Anaplasmosis Affect the Brain? Neurologic Symptoms and Recovery

Can Anaplasmosis Cause Heart Problems? Myopericarditis and Atrial Fibrillation

Anaplasmosis and Lyme Disease: Symptoms, Lab Findings, and Treatment

Babesia vs Anaplasmosis: Symptoms, Diagnosis, and Treatment

References

1. Dumic I, Schultz M, Benny C, Rich J, Shiari A. Comparative Clinical Characteristics of ICU and Non-ICU Hospitalized Patients With Human Anaplasmosis. Open Forum Infect Dis. 2026;13(5):ofag313. doi:10.1093/ofid/ofag313. PMID: 42231944; PMCID: PMC13223063.
2. Aydin Y, Vemuri B, Ahmed SM, Elgamal M, Bilgin S. Severe Anaplasmosis With Multiorgan Involvement in a Rheumatoid Arthritis Patient. Cureus. 2023;15(7):e41536. doi:10.7759/cureus.41536. PMID: 37554613; PMCID: PMC10404564.
3. Dumler JS. The Biological Basis of Severe Outcomes in Anaplasma phagocytophilum Infection. FEMS Immunol Med Microbiol. 2012;64(1):13–20. doi:10.1111/j.1574-695X.2011.00909.x. PMID: 22098465; PMCID: PMC3256277.
4. Abraham JD, Wenning HS, Saeed DA, Derbarsegian A, Brook BA, He P. Becoming Endemic: Anaplasmosis Imported Across State Borders. Cureus. 2024;16(4):e57902. doi:10.7759/cureus.57902. PMID: 38725788; PMCID: PMC11079709.
5. Ismail N, McBride JW. Tick-Borne Emerging Infections: Ehrlichiosis and Anaplasmosis. Clin Lab Med. 2017;37(2):317–340. doi:10.1016/j.cll.2017.01.006. PMID: 28457353.
6. Dixon DM, Branda JA, Clark SH, et al. Ehrlichiosis and Anaplasmosis Subcommittee Report to the Tick-Borne Disease Working Group. Ticks Tick Borne Dis. 2021;12(6):101823. doi:10.1016/j.ttbdis.2021.101823. PMID: 34517150.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention