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dx.
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Myelofibrosis
Cardiovascular Presentations
Abdominal aortic aneurysm
Acute coronary syndrome (NSTEMI)
Acute coronary syndrome (STEMI)
Acute decompensated heart failure
Acute limb ischemia
Acute mesenteric ischemia
Aortic dissection
Aortic stenosis
Atrial fibrillation and flutter
Bradyarrhythmia and heart block
Cardiac arrest
Deep vein thrombosis
Myocarditis
Pericarditis
Pulmonary embolism
Stable angina
Superficial thrombophlebitis
Superior vena cava syndrome
Supraventricular tachycardia
Syncope (cardiogenic)
Unstable angina
Ventricular tachycardia
Respiratory Presentations
Acute bronchitis
Acute respiratory failure
Aspiration pneumonia
Asthma exacerbation
Bronchiolitis
Community-acquired pneumonia
COVID-19 pneumonia
COPD exacerbation
Croup
Croup (laryngotracheobronchitis)
Epiglottitis
Hemothorax
Hospital-acquired pneumonia
Pleural effusion
Pneumothorax (traumatic)
Pulmonary contusion
Spontaneous pneumothorax
Neurological Presentations
Bell's palsy
Benign paroxysmal positional vertigo
Brain abscess
Cauda equina syndrome
Cervical radiculopathy
Concussion (mild traumatic brain injury)
Encephalitis
Guillain-Barré syndrome
Hemorrhagic stroke (intracerebral)
Ischemic stroke
Lumbar radiculopathy
Malignant spinal cord compression
Migraine
Peripheral neuropathy (acute)
Retropharyngeal abscess
Schizophrenia (acute exacerbation)
Seizure (breakthrough:known epilepsy)
Seizure (first-time)
Spinal cord injury
Status epilepticus
Subarachnoid hemorrhage
Tension headache
Transient ischemic attack
Traumatic brain injury (moderate-severe)
Vestibular neuritis
Viral meningitis
Gastrointestinal Presentations
Acute appendicitis
Acute cholecystitis
Acute diverticulitis
Acute pancreatitis
Anal fissure
Choledocholithiasis and cholangitis
Clostridioides difficile colitis
Gastritis
Gastroenteritis (viral and bacterial)
Gastroesophageal reflux disease
Incarcerated or strangulated hernia
Inflammatory bowel disease flare
Large bowel obstruction
Lower GI hemorrhage
Peptic ulcer disease
Perforated viscus
Small bowel obstruction
Upper GI hemorrhage
Genitourinary and Reproductive Presentations
Acute prostatitis
Acute urinary retention
Ectopic pregnancy
Epididymitis
Orchitis
Ovarian torsion
Paraphimosis
Pelvic inflammatory disease
Priapism
Pyelonephritis
Renal laceration
Ruptured ovarian cyst
Testicular torsion
Tubo-ovarian abscess
Urinary tract infection (uncomplicated)
Urolithiasis (renal colic)
Vaginal bleeding (non-pregnant)
Infectious Disease Presentations
Acute sinusitis
Acute tonsillitis
Acute upper respiratory infection
Animal bite
Bacterial meningitis
Cellulitis
Conjunctivitis (bacterial)
Dental abscess
Endocarditis
Febrile neutropenia
Fournier gangrene
Hand-foot-mouth disease
Hepatitis (acute)
Herpes zoster
HIV-related illness
Human bite
Impetigo
Infected diabetic foot ulcer
Infectious mononucleosis
Influenza
Necrotizing fasciitis
Osteomyelitis
Otitis externa
Parasitic infection
Periorbital cellulitis
Peritonsillar abscess
Scabies
Sepsis
Septic arthritis
Spontaneous bacterial peritonitis
Tick-borne illness (Lyme disease)
Tinea infection
Tuberculosis
Viral exanthem
Wound infection
Trauma Presentations
Achilles tendon rupture
ACL and mceniscus tear
Ankle fracture
Ankle sprain
Burn
Calcaneus fracture
Cervical spine fracture
Clavicle fracture
Dental avulsion
Distal radius fracture
Drowning
Elbow fracture and dislocation
Electrical injury
Facial bone fracture
Facial laceration
Femur fracture
Fingertip amputation
Forearm fracture (radius and ulna)
Frostbite
Hand:finger laceration
Heat exhaustion
Heat stroke
Hip fracture
Humeral shaft fracture
Knee dislocation
Knee sprain
Lightning injury
Mandible fracture
Metacarpal fracture
Metatarsal fracture
Muscle strain
Nasal fracture
Non-accidental trauma
Orbital fracture
Patella fracture
Phalanx fracture (finger)
Proximal humerus fracture
Pulmonary contusion
Rib fracture
Rotator cuff tear (acute traumatic)
Scalp laceration
Scaphoid fracture
Shoulder dislocation
Skull fracture
Splenic laceration
Sternal fracture
Supracondylar pediatric fracture
Tendon laceration (hand:wrist)
Thoracic and lumbar spine fracture
Tibia:fibula fracture
Tibial plateau fracture
Toe fracture
Traumatic epistaxis
Traumatic hyphema
Toxicologic Presentations
Acetaminophen toxicity
Alcohol intoxication
Alcohol withdrawal
Anticholinergic toxicity
Anticoagulant overdose
Benzodiazepine overdose
Benzodiazepine:sedative overdose
Beta-blocker and calcium channel blocker toxicity
Carbon monoxide poisoning
Caustic ingestion
Digoxin toxicity
Drug eruption
Foreign body ingestion
Opioid intoxication
Opioid overdose
Opioid withdrawal
Organophosphate
Salicylate toxicity
Serotonin syndrome
Stimulant intoxication (cocaine, methamphetamine)
Tricyclic antidepressant overdose
Psychiatric Presentations
Acute anxiety
Acute psychosis
Agitation:behavioral emergency
Bipolar disorder
Conversion disorder
Major depressive episode
Neuroleptic malignant syndrome
Suicidal ideation and attempt
Musculoskeletal and Rheumatologic Presentations
Acute low back pain (mechanical)
Bursitis
Cervical radiculopathy
Costochondritis
Gout (acute)
Lumbar radiculopathy
Pseudogout
Tendinitis
Dermatology Presentations
Acute eczema (Eczema acute flare)
Allergic contact dermatitis
Erythema multiforme
Henoch-Schönlein purpura
Pressure injury
Psoriasis (acute flare)
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria (acute)
Environmental and Exposure Presentations
Envenomation (snake, spider, insect)
High-altitude illness
Hypothermia
Hematologic and Oncologic Presentations
Acute chest syndrome
Coagulopathy
Hyperviscosity syndrome
Sickle cell crisis (vaso-occlusive)
Symptomatic anemia
Thrombocytopenia (severe)
Tumor lysis syndrome
Pediatric-Specific Presentations
Bronchiolitis
Croup
Emergency delivery
Febrile seizure
Kawasaki disease
Neonatal jaundice
Neonatal sepsis
Nursemaid's elbow
Pediatric fever 0 to 28 days
Pediatric fever 29 to 60 days
Pediatric fever 61 to 90 days
Pyloric stenosis
Slipped capital femoral epiphysis
Intussusception
Endocrine and Metabolic Presentations
Adrenal crisis
Diabetic ketoacidosis
Hypercalcemia
Hyperosmolar hyperglycemic state
Hypertensive emergency
Hypertensive urgency
Hypoglycemia
Myasthenia gravis crisis
Myxedema coma
Severe hyperkalemia
Severe hyponatremia
Thyroid storm
ENT and Maxillofacial Presentations
Acute laryngitis
Acute otitis media
Acute pharyngitis
Cerumen impaction
Epistaxis (anterior)
Nasal foreign body
Otitis externa
Tympanic membrane perforation
Ophthalmologic Presentations
Acute angle-closure glaucoma
Central retinal artery occlusion
Chemical eye injury
Corneal abrasion
Corneal ulcer
Globe rupture
Ocular foreign body
Orbital cellulitis
Retinal detachment
Obstetric Presentations
Hyperemesis gravidarum
Painful vaginal bleeding in pregnancy
Placenta previa
Placental abruption
Preeclampsia:eclampsia
Preterm labor
Threatened:inevitable:incomplete abortion
Systemic and Miscellaneous Presentations
Anaphylaxis
Angioedema
Cannabis-induced hyperemesis
Myelofibrosis
POCUS
Procedures
Calculators
Resuscitation
ECG Guide
Back
Clinical Assessment Checklist
Browse categories and answer follow-up questions to refine your symptom profile.
Approach to the Critical Patient
Immediate priorities
Life-threatening presentations of myelofibrosis
▶
Blast crisis (leukemic transformation)
▶
Peripheral blast count >= 20% defines blast phase
Occurs in ~15% within 5 years of diagnosis
Urgent hematology consult and bone marrow evaluation
Severe anemia with hemodynamic compromise
▶
Hemoglobin <8 g/dL with symptomatic hypoxia
Median survival ~2.1 years with Hgb <8 g/dL
Transfusion threshold individualized to symptoms and cardiopulmonary reserve
Splenic infarction
▶
Acute severe LUQ pain with peritoneal signs
CT abdomen with contrast for confirmation
Pain management and urgent surgical/hematology consult
JAK inhibitor withdrawal syndrome
▶
Fever, respiratory distress, hypotension after abrupt discontinuation
Multi-organ failure risk
Reinstate JAK inhibitor and supportive care urgently
Escalation triggers
Critical thresholds requiring escalation
▶
Hemodynamic instability
▶
SBP <90 mmHg
MAP <65 mmHg
Tachycardia with hemoglobin <70 g/L
Respiratory compromise
▶
Dyspnea at rest with SpO2 <92%
Pulmonary hypertension from extramedullary hematopoiesis
Pleural effusion with respiratory embarrassment
Neurologic emergency
▶
Spinal cord compression from extramedullary hematopoiesis
New focal neurologic deficits
MRI spine urgently if cord compression suspected
Thrombotic or hemorrhagic emergency
▶
Portal hypertension with variceal bleeding
Platelet count <20 × 10^9/L with active bleeding
Arterial or venous thrombosis
Immediate consults
Consultation triggers
▶
Hematology/oncology
▶
All confirmed or suspected MF presentations
Blast phase transformation
Treatment initiation or modification decisions
Interventional radiology or surgery
▶
Splenic infarction with complications
Variceal bleeding
Portal hypertension management
Radiation oncology
▶
Splenic irradiation consideration for refractory splenomegaly
Extramedullary hematopoiesis causing cord compression
Transplant medicine
▶
Intermediate-2 or high-risk disease
Age and comorbidity eligibility assessment
History
Presenting symptoms
Cardinal constitutional symptoms
▶
Fatigue
▶
Present in ~85% of patients
Most debilitating and functionally limiting symptom
Night sweats
▶
Drenching quality distinguishes MPN-related from infectious
Unexplained fevers
▶
Low-grade persistent pattern
Unintentional weight loss
▶
>10% body weight in 6 months carries prognostic significance
Bone pain
▶
Diffuse extremity pain from extramedullary hematopoiesis
Abdominal symptoms
▶
Early satiety
▶
Mechanical compression from progressive splenomegaly
Left upper quadrant pain or fullness
▶
Increasing with progressive splenomegaly
Diarrhea
▶
Gastrointestinal involvement
Alarm features
High-risk presentations
▶
Acute severe LUQ pain
▶
Splenic infarction until proven otherwise
Peritoneal signs suggest rupture risk
Sudden onset dyspnea
▶
Pulmonary hypertension from extramedullary hematopoiesis
Pleural effusion
Severe rapid-onset anemia
New neurologic symptoms
▶
Back pain with weakness or sensory loss suggests cord compression
Extramedullary hematopoiesis in epidural space
Symptoms of blast transformation
▶
Rapid worsening cytopenias
New fever with rising blast count
Rapid spleen enlargement
Risk factor history
Predisposing factors
▶
Age
▶
Most commonly diagnosed between 50 and 80 years
Rare in those under 40 years
Prior myeloproliferative neoplasm
▶
Polycythemia vera transforms to post-PV MF
Essential thrombocythemia transforms to post-ET MF
Duration of antecedent MPN relevant
Family history
▶
Familial clustering of MPNs recognized
First-degree relatives have increased MPN risk
Cardiovascular comorbidities
▶
Contribute to thrombotic complications
Affect treatment tolerability
Medication and treatment history
Current and prior therapies
▶
JAK inhibitor use
▶
Ruxolitinib, fedratinib, pacritinib, or momelotinib
Duration of response and reasons for discontinuation
Risk of withdrawal syndrome with abrupt stopping
Cytoreductive agents
▶
Hydroxyurea history and response
Peginterferon alfa-2a
Anemia-directed therapies
▶
Erythropoiesis-stimulating agents if EPO <500 mU/mL
Danazol use and monitoring compliance
Luspatercept
Transfusion history
▶
Transfusion dependence is a key prognostic variable
Number of units per month baseline
Physical Exam
Vitals and general appearance
Vital sign assessment
▶
Temperature
▶
Low-grade fever from constitutional inflammation
High fever prompts infection workup in immunocompromised state
Heart rate
▶
Tachycardia proportional to anemia severity
Resting HR >100 suggests hemodynamically significant anemia
Blood pressure
▶
Hypotension with severe anemia or bleeding
Hypertension may reflect prior JAK2-driven PV
Weight and BMI
▶
Cachexia and weight loss
Document against prior recorded weights
Abdominal exam
Splenomegaly assessment
▶
Present in nearly all patients with established MF
▶
Measure distance from left costal margin in cm
Massive splenomegaly defined as >10 cm below costal margin
Spleen palpation technique
▶
Dullness to percussion in Traube's space
May extend to right iliac fossa in massive cases
Hepatomegaly
▶
Extramedullary hematopoiesis in liver
Document liver span
Ascites and portal hypertension signs
▶
Ascites
▶
Fluid wave and shifting dullness
Portal hypertension from splenic vein obstruction
Caput medusae
▶
Periumbilical venous engorgement
Indicates portal hypertension
Skin and lymph node exam
Skin findings
▶
Pallor
▶
Conjunctival, palmar, and mucosal pallor from anemia
Petechiae and ecchymoses
▶
Thrombocytopenia-related
Mucosal hemorrhage with severe thrombocytopenia
Pruritus excoriations
▶
Aquagenic pruritus from MPN-related mast cell activation
New skin lesions
▶
Non-melanoma skin cancer risk increased on JAK inhibitors
Annual dermatology surveillance recommended
Lymphadenopathy
▶
Generally not prominent in MF
▶
Significant lymphadenopathy raises concern for lymphoma or transformation
Biopsy if unexplained progressive adenopathy
Musculoskeletal and neurologic exam
Bone tenderness
▶
Diffuse bone pain from marrow expansion and fibrosis
▶
Sternal and long bone tenderness
Joint swelling
▶
Gout from hyperuricemia in high cell turnover states
Neurologic screening
▶
Lower extremity weakness
▶
Cord compression from epidural extramedullary hematopoiesis
Urgent MRI spine if focal deficits present
Sensory level
▶
Dermatomal distribution suggests structural cord pathology
Differential Diagnosis
Myeloproliferative and myeloid disorders
BCR-ABL1-positive disorders
▶
Chronic myeloid leukemia (CML)
▶
ICD-10 C92.1
Must exclude with BCR::ABL1 FISH or RT-PCR — mandatory in workup
Similar splenomegaly and leukocytosis pattern
Distinguishing features
▶
CML has BCR::ABL1 fusion; MF does not
Philadelphia chromosome present in CML
BCR-ABL1-negative MPNs
▶
Polycythemia vera
▶
ICD-10 D45
Distinguished by erythrocytosis and JAK2 V617F
Post-PV MF develops after established PV course
Essential thrombocythemia
▶
ICD-10 D47.3
Distinguished by isolated thrombocytosis without fibrosis early
Post-ET MF distinguished by characteristic bone marrow morphology
Bone marrow failure and malignancy
Myelodysplastic syndromes
▶
MDS with fibrosis
▶
ICD-10 D46.9
Can have reticulin fibrosis
Distinguished by dysplastic morphology and cytogenetics
MDS/MPN overlap syndromes
▶
Chronic myelomonocytic leukemia (CMML) can develop monocytosis mimicking MF
ICD-10 C93.1
Acute leukemia
▶
Acute myeloid leukemia (AML)
▶
ICD-10 C92.0
Blast crisis of MF is classified as AML
>= 20% blasts defines transformation
Systemic mastocytosis
▶
ICD-10 D47.0
▶
Mast cell aggregates on bone marrow biopsy
Tryptase level elevated
Reactive and secondary fibrosis
Secondary bone marrow fibrosis
▶
Autoimmune disorders
▶
Systemic lupus erythematosus, scleroderma
Antinuclear antibody panel assists distinction
Metastatic malignancy to bone marrow
▶
Breast, prostate, lung most common
Leukoerythroblastosis possible but driver mutation absent
Infectious causes
▶
Miliary tuberculosis, HIV
Hairy cell leukemia mimics with pancytopenia and fibrosis
ICD-10 D75.81 for myelofibrosis as general code
Laboratory Tests
Hematologic core labs
Complete blood count with differential
▶
Anemia pattern
▶
Normocytic or macrocytic anemia typical
Hemoglobin <100 g/L common at diagnosis
Hemoglobin <80 g/L indicates high-risk category
White blood cell count
▶
Leukocytosis or leukopenia depending on disease phase
WBC >25 × 10^9/L carries prognostic weight in DIPSS
Platelet count
▶
Thrombocytopenia <100 × 10^9/L in ~30% at diagnosis
Platelets <50 × 10^9/L restricts ruxolitinib; pacritinib indicated
Peripheral blood smear
▶
Leukoerythroblastosis
▶
Nucleated red blood cells (normoblasts) in circulation
Immature granulocytes (myelocytes, metamyelocytes)
Hallmark of bone marrow infiltration or fibrosis
Teardrop cells (dacrocytes)
▶
Classic finding in myelofibrosis
Formed as RBCs are forced through fibrotic marrow
Blast percentage
▶
>10% suggests accelerated phase
>= 20% defines blast phase transformation
Biochemical and prognostic labs
Metabolic panel
▶
Lactate dehydrogenase (LDH)
▶
Elevated LDH is a minor diagnostic criterion for MF
Reflects high cell turnover
Uric acid
▶
Hyperuricemia from increased purine catabolism
Gout risk; allopurinol prophylaxis may be warranted
Liver function tests
▶
Transaminase elevation from hepatic extramedullary hematopoiesis
Bilirubinemia if hemolysis component present
Molecular testing
▶
Driver mutation panel
▶
JAK2 V617F present in ~60% of MF cases
CALR exon 9 mutations in ~25% of MF cases
MPL W515L/K in ~5% of MF cases
Triple-negative (no JAK2/CALR/MPL) in ~8-10%, worst prognosis
High-molecular-risk mutation panel
▶
ASXL1 mutation associated with inferior survival
EZH2, SRSF2, IDH1/2, TP53, U2AF1 Q157
Multigene NGS panel recommended for full prognostic assessment
BCR::ABL1 testing
▶
FISH or RT-PCR mandatory to exclude CML
Supplementary diagnostics
Erythropoietin level
▶
Guide ESA eligibility
▶
EPO <500 mU/mL predicts ESA response
Darbepoetin or epoetin alfa considered if low endogenous EPO
Iron studies
▶
Serum iron, TIBC, ferritin
▶
Identify concurrent iron deficiency as contributing cause of anemia
Ferritin elevated with chronic inflammation (unreliable iron stores indicator)
Coagulation panel
▶
PT and APTT baseline
▶
Acquired coagulation factor abnormalities possible
Von Willebrand factor assay
▶
Acquired von Willebrand syndrome with markedly elevated platelets
Consider if unexplained bleeding despite adequate platelet count
Renal function and electrolytes
▶
Creatinine and GFR
▶
Required for JAK inhibitor dose adjustment
Ruxolitinib dose reduces with GFR <15 mL/min
Diagnostic Tests
Scoring Systems
Prognostic risk stratification tools
▶
DIPSS (Dynamic International Prognostic Scoring System)
▶
Age >65 years (1 point)
Hemoglobin <100 g/L (2 points)
WBC >25 × 10^9/L (1 point)
Circulating blasts >= 1% (1 point)
Constitutional symptoms (1 point)
Low risk (0 points): median survival >15 years
Intermediate-1 (1-2 points): median survival 6.5 years
Intermediate-2 (3-4 points): median survival 2.9 years
High risk (5-6 points): median survival 1.3 years
DIPSS-Plus
▶
Adds karyotype, platelet count, and transfusion status to DIPSS
Unfavorable karyotype adds 1 point
Platelet count <100 × 10^9/L adds 1 point
Transfusion dependence adds 1 point
MIPSS70+v2.0
▶
Integrates molecular mutation data for refined prognostication
High-molecular-risk mutations worsen score
More precise than DIPSS for transplant decision-making
GIPSS (Genetically Inspired Prognostic Scoring System)
▶
Purely genomic-based: karyotype and driver mutations
Does not require clinical variables
MTSS (Myelofibrosis Transplant Scoring System)
▶
Guides hematopoietic cell transplant candidacy assessment
Integrates age, comorbidities, and disease variables
Symptom burden quantification
▶
MPN-SAF TSS (Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score)
▶
10-item patient-reported outcome tool
Scores fatigue, night sweats, itching, abdominal discomfort, early satiety, pain under ribs, bone pain, weight loss, fever, inactivity
Baseline and monitoring assessment to guide treatment
Score >44 associated with significantly reduced quality of life
MRI
MRI indications in myelofibrosis
▶
Spinal cord compression evaluation
▶
New neurologic symptoms with MF diagnosis
Epidural extramedullary hematopoiesis detected on MRI spine
Gadolinium-enhanced for best characterization
Bone marrow characterization
▶
MRI marrow signal reflects cellularity and fibrosis
T1 hypointense marrow signal with diffuse fibrosis
Research utility; not required for routine diagnostic workup
Extramedullary hematopoiesis sites
▶
Paraspinal and epidural masses
Intracranial extramedullary hematopoiesis (rare)
Hepatic and splenic signal assessment
Limitations
▶
Not required for routine MF monitoring
Availability and cost constraints in acute setting
CT
CT abdomen and pelvis
▶
Spleen and liver volumetrics
▶
Quantitative spleen volume measurement
>= 35% spleen volume reduction is key treatment response endpoint
Baseline and post-treatment comparison
Splenic infarction
▶
CT with IV contrast identifies wedge-shaped perfusion defect
Indicated for acute severe LUQ pain
Assess for subcapsular hematoma or splenic rupture
Portal hypertension complications
▶
Ascites quantification
Varices identification (mesenteric, splenic, retroperitoneal)
Splenoportal axis patency
CT chest
▶
Pulmonary hypertension workup
▶
Main pulmonary artery diameter >29 mm suggests PH
Right heart enlargement pattern
Pleural effusion characterization
▶
Extramedullary hematopoiesis in pleural space
Volume and complexity assessment
Extramedullary hematopoiesis in thorax
▶
Paraspinal masses
Mediastinal soft tissue deposits
Ultrasound
Abdominal ultrasound
▶
Splenomegaly quantification
▶
Longitudinal splenic diameter >13 cm defines splenomegaly
Serial measurements for treatment response monitoring
First-line imaging for routine surveillance
Hepatomegaly assessment
▶
Liver span measurement
Echogenicity changes with infiltration
Portal vein Doppler
▶
Portal vein thrombosis detection
Hepatopetal vs hepatofugal flow
Reversal of flow indicates severe portal hypertension
Targeted point-of-care ultrasound
▶
Pleural effusion
▶
Identify effusion amenable to thoracentesis
Real-time guidance for thoracentesis
Ascites
▶
Confirm free fluid
Guide diagnostic paracentesis
Septations may indicate complicating infection
Disposition
Inpatient admission criteria
Indications for hospital admission
▶
Hematologic emergency
▶
Blast crisis transformation
Symptomatic anemia requiring transfusion (Hgb <70-80 g/L)
Severe thrombocytopenia with bleeding (platelets <20 × 10^9/L)
Febrile neutropenia in setting of immunosuppression
Complications requiring acute management
▶
Splenic infarction
Variceal or gastrointestinal hemorrhage
Cord compression from extramedullary hematopoiesis
JAK inhibitor withdrawal syndrome
Systemic compromise
▶
Hemodynamic instability
Respiratory compromise from pleural effusion or pulmonary hypertension
ICU admission criteria
High-acuity indicators
▶
Hemorrhagic shock
▶
Variceal bleeding requiring resuscitation
Spontaneous splenic rupture
Blast crisis with multi-organ compromise
▶
Leukostasis from very high blast count
DIC from AML transformation
Respiratory failure
▶
Pulmonary hypertension with acute decompensation
Massive pleural effusion with respiratory distress
SpO2 <90% despite supplemental oxygen
Outpatient management and follow-up
Copy
Criteria for outpatient management
▶
Hemodynamically stable with no acute complications
▶
Hemoglobin adequate for symptom control
Platelets sufficient to prevent spontaneous bleeding
Established hematology care plan in place
▶
JAK inhibitor management ongoing
Scheduled transfusion program if transfusion-dependent
Follow-up requirements
▶
Hematology every 4-12 weeks depending on disease stability
▶
CBC monitoring on JAK inhibitors
Symptom burden reassessment with MPN-SAF TSS
Annual dermatology review on JAK inhibitors
▶
Non-melanoma skin cancer surveillance
Lipid monitoring every 6 months on ruxolitinib
Transplant consultation referral for intermediate-2 or high-risk patients
Treatment
Risk-stratified treatment approach
Low and intermediate-1 risk disease
▶
Watch and wait for asymptomatic patients
▶
Monitoring CBC every 3-6 months
No proven benefit of early cytoreduction in asymptomatic low-risk
Symptom-directed therapy
▶
Symptomatic splenomegaly or constitutional symptoms guide initiation
Anemia-directed therapy if Hgb <100 g/L and symptomatic
JAK inhibitor consideration
▶
Ruxolitinib for symptomatic disease regardless of risk category
Class I recommendation from NCCN for symptomatic intermediate-1
Intermediate-2 and high-risk disease
▶
Allogeneic hematopoietic cell transplant (allo-HCT)
▶
Only potentially curative therapy for MF
Transplant referral for eligible patients
MTSS score guides selection
Reduced intensity conditioning regimens extend eligibility to older patients
Bridge to transplant with JAK inhibitor
▶
Spleen reduction and symptom control prior to HCT
Pretransplant JAK inhibitor may improve engraftment
JAK inhibitor therapy
Ruxolitinib (Jakafi)
▶
First-line for intermediate/high-risk MF
▶
Approved for MF with platelets >= 50 × 10^9/L
~42% achieve >= 35% spleen volume reduction at week 24
Significant improvement in constitutional symptoms and quality of life
Dosing by platelet count
▶
Platelets >= 200 × 10^9/L: 20 mg orally twice daily
Platelets 100-199 × 10^9/L: 15 mg orally twice daily
Platelets 50-99 × 10^9/L: 5 mg orally twice daily
Dose adjustments
▶
Reduce dose with renal impairment (GFR <15 mL/min)
Titrate based on efficacy and cytopenias
Do not abruptly discontinue; taper over 1-2 weeks to avoid withdrawal
Monitoring
▶
CBC every 2-4 weeks until stable
Infection surveillance (CMV, HBV reactivation risk)
Non-melanoma skin cancer annual dermatology exam
Lipid panel every 6 months
Fedratinib (Inrebic)
▶
Second-line after ruxolitinib failure or intolerance
▶
Approved for intermediate-2 and high-risk MF
Effective spleen volume reduction in ruxolitinib-refractory patients
Dosing
▶
400 mg orally once daily with food
Thiamine supplementation required (risk of Wernicke encephalopathy)
CBC and renal function monitoring
Side effects
▶
Diarrhea and nausea common (take with food and antiemetics)
Wernicke encephalopathy risk; check thiamine levels before initiation
Pacritinib (Vonjo)
▶
Specifically indicated for MF with platelets <50 × 10^9/L
▶
Only JAK inhibitor approved for severe thrombocytopenia
Phase 3 PERSIST-2 and PAC203 trial data
Dosing
▶
200 mg orally twice daily
No dose adjustment required for severe thrombocytopenia
Cardiac monitoring
▶
QT prolongation and arrhythmia risk
Baseline ECG recommended
Momelotinib (Ojjaara)
▶
MF with anemia (Hgb <100 g/L)
▶
Unique dual mechanism: JAK1/2 plus ACVR1 inhibition
ACVR1 inhibition reduces hepcidin, improving iron-restricted erythropoiesis
Simultaneously addresses anemia, splenomegaly, and constitutional symptoms
Dosing
▶
200 mg orally once daily
Peripheral neuropathy monitoring required
Anemia-directed therapies
Erythropoiesis-stimulating agents
▶
Epoetin alfa or darbepoetin alfa
▶
Indicated when endogenous EPO <500 mU/mL
Darbepoetin alfa 150-300 mcg subcutaneously every 1-3 weeks
Response assessment at 12 weeks
Avoid if platelets >600 × 10^9/L (thrombosis risk)
Luspatercept
▶
Erythroid maturation agent
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1 mg/kg subcutaneously every 3 weeks
Titrate to maximum 1.75 mg/kg if no response
Evidence in transfusion-dependent MF patients
Danazol
▶
Androgenic agent for anemia
▶
200 mg orally 2-3 times daily
Monitor liver function tests (hepatotoxicity risk)
Prostate cancer screening in males before initiation
Avoid concurrent statins (rhabdomyolysis risk)
Red blood cell transfusion
▶
Threshold individualized
▶
Symptomatic anemia trigger (not a fixed hemoglobin)
Pre-transfusion Hgb typically <70-80 g/L in stable patients
Leukocyte-depleted irradiated blood products for transplant candidates
Iron chelation therapy if >20 lifetime transfusions (serum ferritin >1000 mcg/L)
Cytoreductive and other therapies
Hydroxyurea
▶
Cytoreduction for symptomatic leukocytosis or thrombocytosis
▶
500-2000 mg orally daily in divided doses
Titrate to CBC response
Skin ulcers and macrocytosis as side effects
Peginterferon alfa-2a
▶
Early-stage or low-risk disease option
▶
45-135 mcg subcutaneously weekly
May reduce JAK2 allele burden
Autoimmune and mood side effects limit use
Spleen-directed therapies
▶
Splenic irradiation
▶
Symptomatic splenomegaly refractory to systemic therapy
1-2 Gy in 5-10 fractions
Temporary benefit; risk of severe cytopenias
Splenectomy
▶
Refractory splenomegaly with severe symptoms
Significant operative risk in MF (infection, thrombosis, portal hypertension)
Postoperative thrombocytosis and hepatomegaly risk
Special Populations
Pregnancy
Pregnancy in myelofibrosis
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Epidemiology
▶
MF in reproductive-age females is rare; most diagnoses are post-menopausal
Reported cases show high fetal and maternal complication rates
Maternal risks
▶
Thrombosis and hemorrhage with thrombocytopenia
Progressive anemia worsening with pregnancy demands
Portal hypertension and variceal hemorrhage risk from splenomegaly
Fetal risks
▶
First trimester loss is increased
Intrauterine growth restriction from placental thrombosis
Treatment considerations
▶
JAK inhibitors contraindicated in pregnancy (teratogenicity)
Hydroxyurea is teratogenic and contraindicated
Peginterferon alfa-2a is relatively contraindicated; limited pregnancy data
Low-dose aspirin and LMWH may be used for thromboprophylaxis
Red blood cell transfusion for symptomatic anemia (target Hgb >80 g/L)
Fetal monitoring and high-risk obstetric co-management essential
Postpartum
▶
Restart or initiate JAK inhibitor promptly postpartum if needed
Breastfeeding is contraindicated with JAK inhibitor use
Geriatric
Older adult considerations in myelofibrosis
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Disease demographics
▶
Median age at diagnosis 65-70 years
Most MF patients are in the geriatric age range
Comorbidity burden is high and affects treatment tolerance
Transplant eligibility
▶
Reduced-intensity conditioning regimens extend HCT eligibility to age 70-75
Comprehensive geriatric assessment for transplant candidacy
MTSS score integrates age as key variable
JAK inhibitor dosing
▶
Renal impairment common; ruxolitinib dose adjustment required
Polypharmacy interactions with JAK inhibitors (CYP3A4 interactions with fedratinib)
Increased infection risk in immunosenescent patients
Anemia management
▶
ESAs less effective in comorbidity-heavy older patients
Transfusion dependence more common
Iron chelation considerations with ferritin >1000 mcg/L
Falls and functional assessment
▶
Anemia and bone pain contribute to fall risk
Functional assessment guides aggressive vs palliative intent
Palliative and goals of care
▶
High-risk older patients with multiple comorbidities may prefer symptom-focused care
Palliative JAK inhibitor therapy to reduce splenomegaly and constitutional symptoms
Pediatrics
Pediatric myelofibrosis
▶
Epidemiology
▶
Primary MF is exceedingly rare in children
Pediatric myelofibrosis more often secondary to other conditions
Juvenile myelomonocytic leukemia (JMML) can mimic MF
Etiology differences
▶
Autoimmune myelofibrosis: immune-mediated, potentially reversible
Associated with autoimmune disorders (lupus, hemolytic anemia)
Metabolic and storage disorders (Gaucher, osteopetrosis)
Diagnosis approach
▶
Bone marrow biopsy required
Genetic and metabolic workup differs from adult MF
JAK2 and CALR mutations uncommon in pediatric primary MF
Treatment
▶
Autoimmune MF: immunosuppression (corticosteroids, cyclosporine) may reverse fibrosis
Allogeneic HCT is treatment of choice for primary pediatric MF
Ruxolitinib has been used in children; weight-based dosing per clinical guidance
Pediatric hematology/oncology referral mandatory
Prognosis
▶
Autoimmune MF has better prognosis than primary MF in children
Primary pediatric MF often rapidly progressive
Background
Epidemiology
Incidence and prevalence
▶
Incidence rate approximately 0.5-1.5 per 100,000 persons per year
▶
Primary MF accounts for the majority of cases
Post-PV MF and post-ET MF account for secondary MF
Age distribution
▶
Median age at diagnosis 65-70 years
Rare below age 40; more aggressive course when occurring in younger patients
Sex distribution
▶
Slight male predominance in primary MF
Post-ET MF may be more common in females given higher ET prevalence
Survival heterogeneity
▶
Low-risk: median survival >15 years
Intermediate-1: median survival 6.5 years
Intermediate-2: median survival 2.9 years
High-risk: median survival 1.3 years
Leukemic transformation
▶
Blast crisis occurs in ~15% within 5 years
▶
Median survival after transformation <6 months with chemotherapy
High-molecular-risk mutations predict higher transformation rate
IDH1/2 and SRSF2 mutations particularly associated with transformation
Pathophysiology
Clonal origin and driver mutations
▶
Origin in hematopoietic stem cell clone
▶
BCR-ABL1-negative clonal myeloproliferation
Driver mutations activate JAK-STAT signaling pathway
JAK2 V617F mutation (~60% of cases)
▶
Point mutation in pseudokinase domain of JAK2
Constitutive activation of JAK-STAT signaling
Promotes unregulated proliferation of myeloid progenitors
CALR mutations (~25% of cases)
▶
Exon 9 frameshift insertions or deletions
Mutant calreticulin activates MPL (thrombopoietin receptor)
Predominantly type 1 (del52) and type 2 (ins5) mutations
MPL mutations (~5% of cases)
▶
W515L/K point mutations in thrombopoietin receptor
Also constitutively activate JAK-STAT pathway
Triple-negative MF (~8-10% of cases)
▶
No JAK2, CALR, or MPL driver mutation
Worst prognosis; may harbor non-canonical mutations
Bone marrow fibrosis mechanism
▶
Abnormal megakaryocyte proliferation and apoptosis
▶
Megakaryocytes release TGF-beta, PDGF, and VEGF
TGF-beta is the primary driver of reticulin and collagen fibrosis
Progressive fibrosis grades from 0 (absent) to 3 (dense collagen)
Osteosclerosis in advanced disease
▶
Trabecular bone thickening
"Dry tap" on aspirate from sclerotic marrow
Extramedullary hematopoiesis
▶
Hematopoietic stem cell egress from fibrotic marrow
▶
Spleen and liver are primary extramedullary hematopoietic sites
Progressive splenomegaly and hepatomegaly
Paraspinal, epidural, pleural, and lymph node sites possible
Consequences
▶
Portal hypertension from splenic congestion and hepatic involvement
Cytopenias from splenic sequestration (hypersplenism)
Leukoerythroblastosis from marrow space compromise
Therapeutic Considerations
JAK inhibitor mechanism and rationale
▶
All three JAK inhibitors target JAK1 and JAK2
▶
Suppress constitutively active JAK-STAT signaling regardless of driver mutation
Effective in triple-negative MF as well as mutation-positive disease
Clinical benefits
▶
Spleen volume reduction reduces hypersplenism and abdominal symptoms
Constitutional symptom improvement through cytokine suppression
Overall survival benefit suggested in landmark COMFORT trials for ruxolitinib
Disease-modifying debate
▶
JAK inhibitors do not eliminate the malignant clone
Allele burden reduction is modest and variable
Allo-HCT remains the only potentially curative approach
Transplant principles
▶
Timing of transplant is critical
▶
Too early: unnecessary transplant-related mortality in lower-risk disease
Too late: poor marrow function and performance status at high-risk stage
Intermediate-2 or high-risk by DIPSS-Plus or MIPSS70+v2.0 triggers referral
JAK inhibitor before transplant
▶
Pretransplant ruxolitinib reduces spleen and inflammatory milieu
May improve transplant outcomes; avoid abrupt discontinuation
Taper ruxolitinib in days before conditioning, not weeks before
High-molecular-risk mutation implications
▶
ASXL1, EZH2, SRSF2, IDH1/2, TP53 mutations
▶
Associated with shorter survival and higher leukemic transformation
IDH1/2 mutations may be targetable with enasidenib or ivosidenib
TP53 mutations predict poor response to standard therapies
Patient Discharge Instructions
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Myelofibrosis home care instructions
▶
Continue all prescribed medications without stopping suddenly
▶
Do not stop JAK inhibitors (ruxolitinib, fedratinib, pacritinib, momelotinib) abruptly
Sudden stopping can cause fever, low blood pressure, and serious illness
Rest and activity
▶
Rest when fatigued; anemia makes energy levels low
Light activity as tolerated; avoid contact sports if platelet count is low
Diet
▶
Small frequent meals if your spleen is large and you feel full quickly
High-protein, high-calorie food to maintain weight
Stay well hydrated, especially if taking hydroxyurea
Skin care on JAK inhibitors
▶
Use sunscreen and check skin regularly for new lesions
Annual skin check with a dermatologist is recommended
Warning signs to return to the emergency department
▶
Sudden severe left-sided abdominal or left shoulder pain
▶
May indicate splenic infarction or rupture
Weakness, numbness, or difficulty walking
▶
May indicate spinal cord compression from the disease
Significant bleeding
▶
Blood in stool, urine, or vomiting blood
Heavy bruising or prolonged bleeding from minor cuts
Fever above 38.5 C (101.3 F)
▶
Infection risk is higher with myelofibrosis and its treatments
Severe shortness of breath or chest pain
Signs of JAK inhibitor withdrawal if medication was missed or stopped
▶
High fever, shaking, low blood pressure, confusion
Extreme fatigue with dizziness or fainting (may indicate sudden anemia worsening)
Follow-up instructions
▶
Keep all scheduled appointments with your hematologist
▶
Blood tests are required frequently to monitor your counts
Report new or worsening symptoms before your next visit
Scheduled transfusion appointments if you are transfusion-dependent
Bone marrow biopsy as scheduled by your specialist
Transplant consultation appointment if referred
Lifestyle and prevention
▶
Infection prevention
▶
Hand hygiene and avoid sick contacts
Stay up to date with vaccinations (discuss with hematologist before live vaccines)
Avoid aspirin and NSAIDs unless prescribed; increased bleeding risk with low platelets
Alcohol moderation; alcohol interacts with fatigue and some medications
References
Guidelines and key sources
Society guidelines
▶
NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms
▶
Current version provides diagnostic criteria, risk stratification, and treatment algorithms
Guides JAK inhibitor selection by platelet count and risk category
European LeukemiaNet (ELN) recommendations for MF
▶
Molecular diagnostic standards
Treatment response criteria
British Society for Haematology guidelines on myelofibrosis
Landmark clinical trials
▶
COMFORT-I and COMFORT-II trials (ruxolitinib vs placebo/best available therapy)
▶
Established ruxolitinib as standard of care for intermediate/high-risk MF
~42% of patients achieved >= 35% spleen volume reduction at week 24
Overall survival benefit observed
JAKARTA and JAKARTA-2 trials (fedratinib)
▶
Established fedratinib efficacy post-ruxolitinib
PERSIST-1, PERSIST-2, PAC203 trials (pacritinib)
▶
Established pacritinib for platelets <50 × 10^9/L
SIMPLIFY-1 and MOMENTUM trials (momelotinib)
▶
Demonstrated anemia benefit via ACVR1 inhibition
Prognostic tools and scoring references
▶
Passamonti F et al. DIPSS validation studies
Gangat N et al. DIPSS-Plus: J Clin Oncol 2011
Guglielmelli P et al. MIPSS70+ and MIPSS70+v2.0
Tefferi A et al. GIPSS: Blood 2018
Coding reference
▶
ICD-10-CM D47.4: Osteomyelofibrosis (primary myelofibrosis)
ICD-10-CM D75.81: Myelofibrosis (general/secondary)
SNOMED CT: Primary myelofibrosis (disorder)
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.
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Myelofibrosis