01Approach to the Critical Patient/attcp67

Immediate priorities

›Recognition of severe tick-borne sepsis

›Febrile illness after Ixodes exposure in endemic area

›Upper Midwest or Northeastern US travel or residence

›Spring to summer seasonality peak May to September

›Cytopenias with transaminitis pattern

›Thrombocytopenia

›Leukopenia with transaminitis

›If clinical suspicion, empiric doxycycline immediately

›Do not await confirmatory testing

›CDC guidance delay increases mortality

›Airway and breathing threats

›Respiratory distress

›ARDS reported in 6.3% of complicated cases

›Hypoxemia with bilateral infiltrates

›Oxygenation failure

›SpO2 < 90% on room air

›PaO2 < 60 mmHg

›If unable to protect airway, proceed to definitive airway control

›Altered sensorium as trigger

›Rapid sequence intubation preparation

›Circulation and shock threats

›Shock physiology

›SBP < 90 mmHg

›MAP < 65 mmHg

›Sepsis screening

›Suspected infection with organ dysfunction

›Lactate >= 2 mmol/l

02History/hx57

Presentation pattern

›Core febrile syndrome

›High fever in 92% to 100%

›Onset 5 to 14 days after tick bite

›Presentation typically 4 to 8 days into illness

›Severe headache in 82%

›Constant and diffuse

›Rarely meningismus

›Malaise in 97%

›Profound fatigue

›Night sweats

›Myalgias in 77%

›Diffuse body aches

›Rigors and chills

›Associated symptoms

›GI symptoms

›Nausea and vomiting

›Diarrhea and anorexia less frequent than ehrlichiosis

›Respiratory symptoms

›Cough

›Dyspnea concerning for ARDS

Exposure history

›Tick exposure

›Known tick bite in 62% to 76% of cases

›Ixodes black-legged deer tick vector

›Incubation 5 to 14 days

›Outdoor activities

›Hiking gardening hunting

03Physical Exam/exam51

Vitals and general

›Stability snapshot

›Temperature

›Often high fever in 92% to 100%

›Hypothermia as severe sepsis marker

›Heart rate and blood pressure

›Tachycardia common

›Hypotension as red flag for shock

›Oxygen saturation

›Room air value

›Desaturation concerning for ARDS

›General appearance

›Ill-appearing and diaphoretic

›Toxic appearance in severe cases

›Rigors at bedside

›Mental status

›Altered sensorium as red flag

›Baseline cognition clarification

Organ-system exam

›Skin survey

›Embedded ticks and bite sites

›Inspect scalp axilla groin popliteal fossa

›Document attachment duration if known

›Rash assessment

›Rash in < 10%

›Erythema migrans suggests Lyme coinfection

›Petechiae or bruising

›Thrombocytopenia correlate

04Differential Diagnosis/ddx37

Tick-borne and infectious mimics

›Other tick-borne illnesses

›Ehrlichiosis E chaffeensis

›Rash more common around 30%

›Morulae in monocytes rather than granulocytes

›Rocky Mountain spotted fever

›Petechial rash starting on wrists and ankles

›Dermacentor vector and more rapidly fatal

›Lyme disease

›Erythema migrans in 70% to 80%

›Same Ixodes vector so coinfection possible

›Babesiosis

›Hemolytic anemia with intraerythrocytic parasites

›Same vector and does not respond to doxycycline

›Non-tick infections

›Viral syndromes

›Influenza EBV CMV

›Early HGA mimicry

›Meningococcemia

›Petechial rash

›Rapid deterioration

›Sepsis from other sources

›Bacterial sepsis with cytopenias

›Transaminitis overlap

Hematologic and noninfectious mimics

›Microangiopathic syndromes

›TTP and HUS

›Thrombocytopenia with MAHA

05Laboratory Tests/lt58

Core labs

›Complete blood count with differential

›Thrombocytopenia in 71% to 95%

›Hallmark finding

›Track for bleeding risk

›Leukopenia in 49% to 59%

›Lymphopenia with left shift

›Mild anemia

›Classic triad present in only 24%

›Leukopenia plus thrombocytopenia plus transaminitis

›Associated with hospitalization OR 1.78

›Hepatic and inflammatory markers

›Comprehensive metabolic panel

›Elevated AST and ALT 2 to 4 times normal in 67%

›Renal function for severity and dosing

›CRP elevation

›Elevated in 100% in one series

›Nonspecific marker

Confirmatory testing

›PCR nucleic acid amplification

›Confirmatory test of choice during acute illness

›Whole blood EDTA tube transport on ice

›Sensitivity > 95% within first 10 days

›Timing dependence

›Highest yield before antibiotics

›Yield falls after doxycycline started

›Peripheral blood smear

›Morulae in neutrophils

06Diagnostic Tests/dt53

Scoring Systems

›Sepsis risk stratification

›qSOFA

›RR >= 22 per minute

›SBP <= 100 mmHg

›Altered mental status

›SIRS criteria

›Temperature and heart rate thresholds

›WBC abnormality which may be low in HGA

›Anaplasma-specific decision support

›Clinical decision support tree

›Platelet count > 177 x 10^3/uL and age < 48 years very unlikely positive PCR

›Optimizes NAAT utilization

›Limitations

›No validated severity score specific to HGA

›Clinical trajectory supersedes single score

MRI

›MRI brain role

›Limited acute utility

›Not required for uncomplicated disease

›Reserved for focal neurologic deficit

›Problem-solving indications

›Persistent encephalopathy

›Exclude alternative CNS process

›Contraindications

›Unstable patient

›Non-compatible implants

07Disposition/dispo42

Level of care selection

›Outpatient management

›Appropriate for majority around 67% in large cohort

›Young immunocompetent patients with mild symptoms

›Able to tolerate oral medications

›Requirements

›Reliable follow-up

›No organ dysfunction

›Admission criteria

›Organ dysfunction

›Acute renal failure

›ARDS or DIC

›Hematologic and hemodynamic instability

›Severe thrombocytopenia with bleeding

›Hemodynamic instability

›Host and intake factors

›Immunocompromised with significant illness

›Inability to tolerate oral medications

›Advanced age with comorbidities

›ICU admission

›Around 7% of hospitalized patients require ICU

›Septic shock

›ARDS or multi-organ failure

›Triggers

›Vasopressor requirement

›Mechanical ventilation

Consultation and follow-up

›Specialist consultation triggers

08Treatment/t61

Initial stabilization

›Resuscitation priorities

›ABCs

›Airway protection if obtunded

›Oxygen for hypoxemia

›IV fluids

›Crystalloid for dehydration

›30 ml/kg for hemodynamic instability

›Empiric therapy timing

›Start doxycycline immediately on suspicion

›Do not wait for confirmatory testing

First-line antimicrobial therapy

›Doxycycline first-line for all ages

›Adults

›Doxycycline 100 mg PO BID

›Duration 10 to 14 days

›Children all ages

›Doxycycline 2.2 mg/kg PO BID

›No tooth staining at recommended dose and duration

›Severe or intolerant of oral

›IV doxycycline 100 mg every 12 hours

›For obtunded or severely ill patients

›Duration rationale

›10 days covers possible Lyme coinfection

›Extend to 14 days for severe disease

›Administration counseling

›Take with food and water

›Reduces GI upset

09Special Populations/sp39

Pregnancy

›Pregnancy considerations

›Doxycycline safety

›Generally avoided in pregnancy

›May be warranted in life-threatening HGA

›Alternative therapy

›Rifampin 300 mg PO BID with limited data

›Infectious disease and obstetrics co-management

›Maternal stabilization

›Maintain SpO2 >= 95% when feasible

›Fetal monitoring when viable gestation

›Coinfection vigilance

›Babesiosis more severe in pregnancy

›Test for Lyme coinfection

Geriatric

›Older adult features

›Higher severity risk

›Median age of hospitalized patients 71 years

›Increased mortality with delayed diagnosis

›Atypical presentation

›Afebrile infection possible

›Delirium as presenting feature

›Medication considerations

›Renal function for dosing

›Review polypharmacy interactions

›Disposition bias

›Lower threshold for admission

›Comorbidity burden

10Background/b52

Epidemiology

›Disease distribution

›Geographic concentration

›VT ME RI MN MA WI NH NY account for 90% of cases

›Also endemic in parts of Europe and Asia

›Demographics

›Male-to-female ratio approximately 2 to 3 to 1

›Older adults higher severe disease risk

›Seasonality

›Spring and summer tick activity peak

›Peak May to September

›Outcomes

›Mortality

›< 1% with appropriate treatment

›Rises with delayed diagnosis in elderly and immunocompromised

›Complication burden

›Reported in up to 40.5% with reporting bias

›Sequelae in only around 2.1% of cases

Pathophysiology

›Organism and transmission

›Causative agent

›Anaplasma phagocytophilum obligate intracellular bacterium

›Infects granulocytes forming morulae

›Vector and incubation

›Ixodes species black-legged deer tick

›Incubation 5 to 14 days

›Disease mechanism

›Granulocyte infection

11Patient Discharge Instructions/pdi21

copy discharge instructions

›Anaplasmosis home care

›Take doxycycline exactly as prescribed until finished

›Complete the full course even if feeling better

›Take with food and water and avoid dairy within 2 hours

›Avoid direct sun and use sunscreen due to photosensitivity

›Rest and drink plenty of fluids

›Warning signs to return to ER

›Fever that persists or returns after 48 hours of antibiotics

›Worsening headache confusion or trouble staying awake

›Shortness of breath or chest pain

›New bleeding bruising or tiny red skin spots

›Inability to keep down medications or fluids

›Follow up

›Clinician follow up within 1 to 2 weeks

›Repeat blood tests to confirm recovery

›Discuss any new tick bites with your clinician

›Tick prevention tips

›Use DEET repellent and permethrin-treated clothing

›Perform daily full-body tick checks after being outdoors

›Remove attached ticks promptly with fine tweezers

›Shower soon after outdoor activity

12References/r13

Guidelines and key sources

›Guideline and society sources

›CDC tickborne rickettsial diseases recommendations and reports MMWR 2016

›Wilderness Medical Society clinical practice guidelines for tick-borne illness 2021

›CDC Tickborne Diseases of the United States reference manual 2022

›Key reviews and studies

›MacQueen and Centellas Human Granulocytic Anaplasmosis Infect Dis Clin North Am 2022

›Sanchez et al Lyme anaplasmosis and babesiosis JAMA 2016

›Katragadda et al trends in anaplasmosis clinical features and outcomes CID 2026

›Schudel et al systematic review of human granulocytotropic anaplasmosis PLoS NTD 2024

›Decision support and coding

›Hamilton et al clinical decision support for Anaplasma NAAT utilization J Clin Microbiol 2021

›Anaplasmosis ICD-10 A77.49 other spotted fever group rickettsioses

›SNOMED CT human granulocytic anaplasmosis disorder concept

Evidence & Review

Evidence & Review