View source for Fanconi anemia

==Background==
*Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome, characterized by progressive [[Pancytopenia|pancytopenia]], congenital anomalies, and markedly increased cancer susceptibility.
*Emergency physicians encounter FA patients presenting with hemorrhagic emergencies, [[Febrile neutropenia|febrile neutropenia]], severe anemia, and malignancy complications.
*Critically, FA patients have extreme sensitivity to DNA-damaging agents — standard-dose chemotherapy and radiation can cause fatal toxicity if FA is undiagnosed.<ref name="StatPearls">Fanconi Anemia. ''StatPearls''. 2024. PMID: 32119428</ref> Not the same as [[Fanconi syndrome]] (a renal tubular disorder).
*Autosomal recessive (most common) or X-linked recessive genetic disorder affecting DNA interstrand crosslink (ICL) repair<ref name="StatPearls"/>
*Mutations in at least 22 FA genes (FANCA most common, ~65% of cases)
*Prevalence approximately 1:350,000 births; carrier frequency ~1:300 in European/US populations<ref name="GeneReviews">Fanconi Anemia. ''GeneReviews''. NCBI. 2026.</ref>
*Higher carrier frequency in Ashkenazi Jewish, Afrikaner, and Spanish Romani populations
*Median age of diagnosis: 6-8 years; ~25% of patients have NO congenital anomalies and may not be diagnosed until adulthood<ref name="Medscape">Fanconi Anemia. ''Medscape''. 2024.</ref>
* 90% develop bone marrow failure by age 40<ref name="GeneReviews"/>
*Median mortality age ~20 years (improving with modern transplant techniques)
*Leading causes of death: bone marrow failure > malignancy (AML/MDS, head/neck squamous cell carcinoma) > complications of transplant

==Clinical features==
===What the EM physician will see===
*FA patients most commonly present to the ED with complications of pancytopenia:

====Hemorrhagic emergencies====
*Epistaxis (often recurrent and severe)
*Mucocutaneous bleeding, petechiae, purpura, ecchymoses
*GI hemorrhage
* Intracranial hemorrhage (particularly dangerous; high-impact activities should be avoided in thrombocytopenic patients)<ref name="FanconiGuidelines">Fanconi Anemia: Guidelines for Diagnosis and Management. 4th ed. Fanconi Anemia Research Fund.</ref>
*Menorrhagia in adolescent/adult females
*Prolonged bleeding from wounds, dental procedures, or minor trauma

====Infectious emergencies====
* [[Febrile neutropenia]] — the most dangerous acute presentation; treat as per standard [[Febrile neutropenia|febrile neutropenia]] protocols
*Recurrent bacterial infections (pneumonia, skin infections, sinusitis, UTIs)
*Oral candidiasis, fungal infections (in severe neutropenia)
*Sepsis

====Anemia-related symptoms====
*Fatigue, weakness, dyspnea on exertion
*Dizziness, syncope, tachycardia
*Pallor
*High-output [[Heart failure|cardiac failure]] (rare, with very severe chronic anemia)

===Congenital anomalies (present in ~75%)===
*Useful for recognizing the undiagnosed FA patient presenting to the ED:
* Skeletal: absent or hypoplastic thumbs, absent/hypoplastic radii (always with thumb abnormalities), short stature, vertebral anomalies
* Skin: café au lait spots (>50%), diffuse hyperpigmentation, hypopigmented patches
* Head: microcephaly (25%)
* Eyes: microphthalmia, strabismus, epicanthal folds
* Ears: hearing loss (usually conductive), low-set or malformed ears
* Renal: structural anomalies (horseshoe kidney, ectopic kidney, absent kidney) — 20%<ref name="GeneReviews"/>
* Cardiac: congenital heart defects — 5%
* GI: tracheoesophageal fistula, esophageal/duodenal atresia, imperforate anus
* Genitourinary: cryptorchidism, hypospadias, micropenis (males); structural uterine/vaginal anomalies (females)
* VACTERL-H phenotype (vertebral, anal, cardiac, tracheoesophageal, renal, limb + hydrocephalus) found in ~12%<ref name="GeneReviews"/>
* 25% of FA patients have NO physical anomalies — suspect FA in any young patient with unexplained pancytopenia

===Malignancy===
* AML/MDS: ~30% lifetime risk; may be the initial presentation of previously undiagnosed FA
* Head and neck squamous cell carcinoma: greatly increased risk, particularly after stem cell transplant and in patients with graft-versus-host disease
* Gynecologic malignancy: vulvar and cervical SCC
* Liver tumors: hepatocellular carcinoma, hepatic adenomas (particularly in patients treated with androgens)
* Critical EM pitfall: if an FA patient presents with leukemia or a solid tumor and is given '''standard-dose chemotherapy or radiation''', '''extreme and potentially fatal myelosuppression''' will result due to impaired DNA repair<ref name="StatPearls"/>

==Differential diagnosis==
===Other inherited bone marrow failure syndromes===
*Dyskeratosis congenita
*Diamond-Blackfan anemia
*Shwachman-Diamond syndrome
*Thrombocytopenia-absent radius (TAR) syndrome

===Other causes of [[Pancytopenia|pancytopenia]]===
*[[Aplastic anemia]] (acquired)
*Myelodysplastic syndrome
*Acute leukemia
*Megaloblastic anemia (B12/folate deficiency)
*HIV
*Drug-induced myelosuppression
*Systemic lupus erythematosus


{{Anemia DDX}}
{{Increased bleeding DDX}}

==Evaluation==
===EM workup (acute presentations)===
* CBC with differential and peripheral smear:
** Macrocytosis (elevated MCV — often the earliest hematologic abnormality; precedes cytopenias)<ref name="GeneReviews"/>
**Elevated fetal hemoglobin (HbF)
**Thrombocytopenia (usually appears first)
**Leukopenia/neutropenia
**Anemia (develops later)
**Smear: macrocytes, occasional target cells; blast cells if AML transformation
* Reticulocyte count: low (hypoproliferative anemia)
* Type and screen — anticipate transfusion needs
* BMP: electrolytes, renal function (structural renal anomalies are common)
* LFTs: hepatic adenomas and iron overload from chronic transfusion
* Coagulation studies: if active bleeding
* Blood cultures (at least 2 sets from separate sites) — before antibiotics if febrile neutropenia
* Urinalysis, chest radiograph — as indicated by clinical presentation
* Lactate, procalcitonin — if sepsis suspected
* ECG — if congenital heart disease or cardiomyopathy suspected

===When to suspect undiagnosed FA in the ED===
*Young patient with unexplained pancytopenia + macrocytosis ± congenital anomalies
*Patient with unexpected severe toxicity from standard-dose chemotherapy or radiation
*Early-onset malignancy (AML in a child/young adult; head/neck SCC in a young non-smoker)
* Diagnosis is confirmed by chromosomal breakage (fragility) test using diepoxybutane (DEB) or mitomycin C — this is not an ED test but should be arranged via hematology consultation<ref name="StatPearls"/>

==Management==
===Hemorrhagic emergencies===
* Platelet transfusion:
** Use single-donor platelets (reduces alloimmunization risk)<ref name="Medscape"/>
** Leukodepleted (CMV risk reduction)
** Irradiated (prevents transfusion-associated graft-versus-host disease)
**'''Do NOT use blood products from family members''' — may sensitize the patient and compromise future stem cell transplantation<ref name="FanconiGuidelines"/>
**Transfuse for active bleeding or platelets <10,000/μL (or <50,000/μL if surgery/invasive procedure planned)
* Avoid:
**NSAIDs and aspirin (impair platelet function)
**IM injections (hematoma risk)
**Rectal thermometers, suppositories, enemas (mucosal trauma)
* Epistaxis: topical hemostatic agents, anterior packing; avoid posterior packing if possible due to mucosal fragility
* Aminocaproic acid (Amicar) or tranexamic acid: may be used as adjunctive antifibrinolytic therapy for mucosal bleeding<ref name="FanconiGuidelines"/>

===Febrile neutropenia===
*Manage per standard '''[[Febrile neutropenia]]''' protocols — this is a medical emergency
*Fever (≥38.3°C single or ≥38.0°C sustained) + ANC <500/μL (or expected to fall below 500/μL)
* Empiric broad-spectrum antibiotics within 1 hour of presentation (e.g., cefepime, piperacillin-tazobactam, or meropenem per institutional protocol)
*Blood cultures before antibiotics (do not delay antibiotics for cultures if not immediately obtainable)
*Low threshold for antifungal coverage if not responding to antibiotics within 48-72 hours
* G-CSF (filgrastim) may be used for neutropenia-related infectious complications with ANC <500/μL<ref name="FanconiGuidelines"/>

===Anemia===
* Packed RBC transfusion:
** Leukodepleted, irradiated (same principles as platelets)<ref name="Medscape"/>
**'''Do NOT use family member donors'''
**Transfusion threshold depends on clinical context; generally for hemoglobin <7 g/dL or symptomatic anemia
* Monitor for transfusional iron overload in chronically transfused patients — serum ferritin, cardiac and hepatic MRI T2*

===Airway considerations===
* Skeletal anomalies (vertebral, mandibular) may make intubation difficult<ref name="Anesthesia">Anesthetic Management of a Patient With Fanconi Anemia. ''Anesth Prog''. 2019;66(4):214-217. doi:10.2344/anpr-D-18-00057</ref>
*Short stature may require smaller-than-expected equipment
* Avoid nasal intubation if thrombocytopenic (nasal bleeding risk)
*Avoid nitrous oxide (suppresses bone marrow via impaired methionine synthetase)<ref name="Anesthesia"/>

===Medication safety===
* Avoid NSAIDs and aspirin
* Avoid IM injections
*FA patients receiving androgens (oxymetholone, danazol) for bone marrow stimulation may have: hepatic dysfunction (peliosis hepatis, adenomas), virilization, lipid abnormalities — consider when interpreting labs
*If cancer is diagnosed or suspected, '''do NOT initiate standard-dose chemotherapy or radiation in the ED''' — consult hematology/oncology experienced in FA management; profoundly reduced doses are required<ref name="StatPearls"/>

==Disposition==
* Febrile neutropenia: admit; ICU if hemodynamically unstable or severely septic
* Active hemorrhage with severe thrombocytopenia: admit to monitored setting; hematology consultation
* Severe anemia (Hb <7 g/dL) or symptomatic: admit for transfusion and evaluation
* New pancytopenia of unknown cause: admit or arrange urgent hematology follow-up; do not discharge without a plan for workup
* Stable known FA patient with mild cytopenias: may discharge with close hematology follow-up and clear return precautions for fever, bleeding, syncope, or worsening weakness
* All FA patients: ensure hematology is involved in care and aware of the ED visit
*Educate patients/families:
**Return immediately for '''any''' fever (even low-grade if neutropenic)
**Avoid contact sports and high-impact activities (head trauma risk with thrombocytopenia)
**Avoid NSAIDs
**Wear medical identification

==See Also==
*[[Fanconi syndrome]] (a completely different condition — renal tubular disorder)
*[[Pancytopenia]]
*[[Febrile neutropenia]]
*[[Aplastic anemia]]
*[[Thrombocytopenia]]
*[[Acute myeloid leukemia]]

==External Links==
*[https://www.ncbi.nlm.nih.gov/books/NBK559133/ StatPearls — Fanconi Anemia]
*[https://www.ncbi.nlm.nih.gov/books/NBK1401/ GeneReviews — Fanconi Anemia]
*[https://fanconi.org/ Fanconi Anemia Research Fund — Clinical Care Guidelines]
*[https://emedicine.medscape.com/article/960401-overview Medscape — Fanconi Anemia]
*[https://rarediseases.org/rare-diseases/fanconi-anemia/ NORD — Fanconi Anemia]

==References==
<references/>

[[Category:Heme/Onc]]
[[Category:Pediatrics]]