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Symptoms to Diagnosis



A 65-YEAR-OLD MAN WITH MELENA AND A BLOOD DISORDER

Monia E. Werlang, MD, Marilia L. Montenegro, MD and Bhaumik Brahmbhatt, MD, MBBS
Cleveland Clinic Journal of Medicine October 2022, 89 (10) 573-578; DOI:
https://doi.org/10.3949/ccjm.89a.20175
Monia E. Werlang
Clinical Assistant Professor, Department of Gastroenterology, University of
South Carolina School of Medicine, Greenville, SC
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Marilia L. Montenegro
Resident, Department of General Surgery, University of Miami, Miami, FL
 * Find this author on Google Scholar
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 * Search for this author on this site

Bhaumik Brahmbhatt
Assistant Professor of Medicine, Division of Gastroenterology and Hepatology,
Mayo Clinic, Jacksonville, FL
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 * For correspondence: Brahmbhatt.Bhaumik@mayo.edu

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A 65-year-old man presented to the emergency department after having 3 black,
tarry bowel movements in the last 24 hours. He had had another episode of melena
4 months earlier, in which upper endoscopy had revealed esophagitis.

For the past 3 years he had chronic anemia related to primary myelofibrosis. The
diagnosis had been confirmed by bone marrow biopsy that showed increased
cellularity (70%–80%), 1.4% blasts, myelofibrosis (graded MF-3 on a scale of
MF-0 to MF-3), normal karyotype, BCR/ABL-negative, and JAK2-positive. He was
being treated with epoetin alfa and ruxolitinib for this condition and needed
blood transfusions every other week. His last transfusion had been earlier in
the day of the bleeding, and his hemoglobin level at that time was 7.6 g/dL
(reference range 13.2–16.6).

The patient also had hypertension, stage 3 chronic kidney disease, vertigo, and
gout. Asked whether he was taking any drugs that could predispose to bleeding
such as anticoagulants, antiplatelet agents, nonsteroidal anti-inflammatory
drugs, or selective serotonin reuptake inhibitors, he said he was not.


PRIMARY MYELOFIBROSIS: A NEOPLASM OF BONE MARROW

1. Which of the following is the most common cause of death in patients with
primary myelofibrosis?

 * Bleeding

 * Cardiovascular complications

 * Leukemic transformation

 * Infection

Primary myelofibrosis is a chronic myeloproliferative neoplasm.1 Its clinical
manifestations are nonspecific and include fever, fatigue, weight loss, and
night sweats. In the absence of symptoms, it is usually discovered in a workup
for anemia, splenomegaly, or hepatomegaly.2 Primary myelofibrosis is classified
as either overtly fibrotic or prefibrotic.

The World Health Organization lists 3 major and 5 minor criteria for
diagnosis.2,3

Major criteria:

 * Megakaryocyte changes

 * JAK2, CALR, or MPL mutations or clonal markers on bone marrow analysis

 * Exclusion of other myeloid neoplasm diagnoses.

Minor criteria:

 * Anemia not otherwise explained

 * Leukocytosis

 * Palpable splenomegaly

 * Increased serum lactate dehydrogenase

 * A leukoerythroblastic blood smear, confirmed in 2 consecutive
   determinations.3

The diagnosis of overt primary myelofibrosis is established if all 3 major
criteria and 1 minor criterion are met.2


CAUSES OF DEATH

The most common causes of death in patients with primary myelofibrosis are
leukemic progression, responsible for up to 20% of deaths,2 followed by
cardiovascular complications, infection, and bleeding.4

There are validated prognostic scoring tools for primary myelofibrosis. Age
older than 65, severity of anemia, degree of leukocytosis, number of circulating
blasts, and presence of constitutional symptoms are associated with worse
survival rates.2


CASE CONTINUED: INITIAL EVALUATION

The patient was awake, oriented, and able to provide a coherent medical history.
He appeared mildly malnourished but with a good general appearance. His pulse
was 104 beats per minute and his blood pressure was 136/57 mm Hg. His spleen was
palpable, and the rims of his conjunctiva were mildly pale. On rectal
examination, his stool was black and tarry. No spider angiomas or jaundice was
noted on physical examination, and there were no signs of ascites on abdominal
examination.

Results of a complete blood cell count and other initial laboratory tests were
as follows:

 * Hemoglobin 6.6 g/dL (reference range 13.2–16.6)

 * Hematocrit 20.8% (38.3%–48.6%)

 * Mean corpuscular hemoglobin 28.4 pg (25.4–32.7)

 * Red blood cell count 2.32 × 1012/L (4.35–5.65)

 * Red cell distribution width 26.9% (11.8%–14.5%)

 * White blood cell count 12.9 × 109/L (3.4–9.6)

 * Platelet count 210 × 109/L (135–317).

 * Glomerular filtration rate 55 mL/min/1.73 m2 body surface area (> 60)

 * Serum creatinine 1.39 mg/dL (0.74–1.35)

 * Total bilirubin 1.3 mg/dL (≤ 1.2)

 * Sodium 140 mmol/L (135–145)

 * Potassium 4.7 mmol/L (3.6–5.2)

 * Chloride 105 mmol/L (98–107)

 * Blood urea nitrogen 29 mg/dL (8–24)

 * Prothrombin time 17.5 seconds (11.6–14.7)

 * International normalized ratio 1.4 (0.8–1.1).

The patient received 2 units of packed red blood cells and an intravenous
proton-pump inhibitor.


DOES THE PATIENT NEED TO BE ADMITTED?

2. Which of the following would not influence the decision whether to admit the
patient to the hospital or perform an outpatient workup?

 * Melena

 * Low hemoglobin level

 * Tachycardia

 * Splenomegaly

Scoring systems are available to help determine the need for hospitalization in
patients with upper gastrointestinal bleeding.

The Glasgow-Blatchford score is recommended by the International Consensus Group
guideline.5 This 23-point score is based on sex, pulse, systolic blood pressure,
blood urea nitrogen, hemoglobin, chronic liver disease, chronic heart disease,
melena, and syncope.6 A score of 0 or 1 is associated with a very low risk of
rebleeding, death, or need for urgent endoscopic intervention.7

The Rockall score, also commonly used,8 is based on clinical components (age,
blood pressure, heart rate, and comorbidities) and endoscopic findings
(diagnosis and bleeding stigmata). However, it is less accurate than the
Glasgow-Blatchford score.9,10

The Glasgow-Blatchford score has been proven for assessing the need for
intervention for both variceal11 and nonvariceal bleeding.12 Different studies
confirmed its accuracy in predicting outcomes.7,10,13 A modified
Glasgow-Blatchford score, which omits the subjective components (comorbidities,
melena, and syncope), has also been shown to perform well.14 These scores do not
consider splenomegaly.

The patient had no history of liver disease, heart failure, or recent syncope or
presyncopal symptoms. His calculated Glasgow-Blatchford score was 12. He was
admitted to the hospital for further evaluation and upper endoscopy.


CASE CONTINUED: UPPER ENDOSCOPY PERFORMED

In view of the patient’s worsening anemia, upper endoscopy was performed.
Findings included 5 columns of spurting, large varices (> 5 mm, grade 3 on a
scale of 3) in the lower third of the esophagus (Figure 1A), and red, dilated
venules (ie, the “red wale” sign). No varices were seen in the stomach, although
there was a substantial amount of clotted blood in the gastric fundus and body,
which could have hidden any varices there. Six bands were placed (Figures 1B,
1C), which partially eradicated the esophageal varices, and the patient was
started on octreotide by continuous infusion for 72 hours. Intravenous
ceftriaxone 1 g was administered approximately 4 hours after the patient
presented to the emergency room, and he received 1 g daily on subsequent days.
He had no further episodes of melena during the hospitalization, and he was
discharged after 4 days.

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Figure 1

Views from the patient’s initial upper endoscopy. (A) Large (grade 3) varices
(circle) in the lower third of the esophagus. (B) Band placement in varices at
the gastric cardia and gastroesophageal junction (circle). (C) Band placement in
varices in the lower third of the esophagus (circle).




MANAGEMENT OF ESOPHAGEAL VARICES

3. Which option is the best next step in managing esophageal varices after
hospitalization?

 * A beta-blocker and follow-up endoscopy in 1 to 4 weeks

 * Abdominal ultrasonography and repeat endoscopy in 1 week

 * A transjugular intrahepatic portosystemic shunt

 * Abdominal ultrasonography and upper endoscopy in 4 to 8 weeks

Hemostasis in esophageal variceal bleeding should preferably be achieved with
variceal band ligation.10 Sclerotherapy should usually be avoided but may be
necessary if visualization is difficult or if there is extensive scarring from
previous banding.15

The management goals for a patient with acute variceal hemorrhage are to avoid
complications and reduce the risk of rebleeding. Red, dilated venules (ie, the
red wale sign) and are considered the endoscopic sign with the highest risk of
rebleeding.16

Secondary prophylaxis after an episode of variceal bleeding can lessen the risk
of death. Initial management includes noncardioselective beta-blockers such as
propranolol, nadolol, and carvedilol. These medications reduce the risk of
esophageal hemorrhage17 and slow the rate of growth of varices.18 The dosage
should be titrated to the highest dose tolerated or to a reduction in the
resting heart rate by 25% or as low as 55 beats per minute. Our patient was
started on carvedilol 6.25 mg daily.

The American Association for the Study of Liver Diseases recommends upper
endoscopy every 2 to 8 weeks until the varices are eradicated, again 3 to 6
months after eradication, and then every 12 months.19,20 Ultrasonography is
recommended in the acute setting to investigate new or worsening ascites in
patients with bleeding esophageal varices, if there is suspicion of portal vein
thrombosis, or to investigate portal hypertension if there is no known history
of liver disease.21

In patients with advanced cirrhosis (Child-Pugh class B or C), placement of a
transjugular intrahepatic portosystemic shunt within the first 3 days after
presentation was shown to reduce the risks of further bleeding and death at 1
year.18,22–25 In general, the major drawback of this treatment is overt hepatic
encephalopathy, which occurs in about one-third of patients. It should be
therefore reserved for select cases.26 In the setting of bleeding esophageal
varices, the ideal candidate for shunt placement within the first 3 days of
presentation would have no history of hepatic encephalopathy, no history of
heart failure or tricuspid valve regurgitation, no signs of sepsis, no pulmonary
hypertension, and no significant coagulopathy.


CASE RESUMED: FURTHER INVESTIGATION

Abdominal ultrasonography was done to evaluate for hepatic or portal vein
thrombosis. The liver was normal in appearance, and blood flow was normal on
Doppler studies. The spleen was markedly enlarged (measuring 24.5 cm), and there
was mild ascites.

Four weeks after discharge, upper endoscopy was performed again and revealed
several varices in the esophagus. The varices were medium-sized (grade 2 on a
scale of 3) and not bleeding, and there were no stigmata of recent bleeding and
no red wale signs. Three bands were placed in the distal 5 cm of the esophagus.
The mucosa of the stomach was diffusely mildly congested, with apparent
extrinsic compression along the greater curvature of the gastric body. In the
second portion of the duodenum, the mucosa appeared swollen with the suggestion
of “ropey” protuberances.

Since Doppler ultrasonography did not show any obvious portal vein thrombosis,
magnetic resonance imaging of the abdomen was performed to evaluate the etiology
of the esophageal varices. This showed cirrhotic liver morphology and hepatic
iron deposition (likely related to transfusions or iron therapy), without
suspicious liver lesions. The hepatic vasculature was patent, with conventional
arterial anatomy and large main portal and splenic veins. Portal hypertension
with moderate ascites and venous collaterals including gastroesophageal varices
were present. The spleen was markedly enlarged, measuring 22.5 cm.


ETIOLOGY OF PORTAL HYPERTENSION

4. What is the most common cause of portal hypertension in the United States?

 * Idiopathic

 * Schistosomiasis

 * Extrahepatic portal venous obstruction

 * Neoplastic occlusion of the intrahepatic portal vein

 * Budd-Chiari syndrome

 * Cirrhosis

Cirrhosis accounts for most cases of portal hypertension in Western countries.27
Noncirrhotic causes account for less than 10% of cases, and they present with
normal synthetic liver function and normal to mildly elevated hepatic venous
pressure gradient.27,28 Common causes of noncirrhotic portal hypertension
include Budd-Chiari syndrome, portal vein thrombosis, and idiopathic portal
hypertension.29 Schistosomiasis, a disease caused by parasitic worms lodging in
the liver, is common in Africa and other tropical areas but not in the United
States.

Causes of portal hypertension are divided according to their anatomic location.
Prehepatic and posthepatic causes differ from intrahepatic disorders in that
they do not directly involve the liver. These disorders cause a disruption in
the hepatic vascular system that leads to increased pressure in the portal
venous system.

Intrahepatic causes are categorized according to where the obstruction is in
relation to the sinusoids, ie, presinusoidal, sinusoidal, or postsinusoidal
(Table 1), although many of them can affect more than one vascular
compartment.30

View this table:
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TABLE 1

Etiology of portal hypertension



Idiopathic portal hypertension has been reported worldwide, but mainly in
developing countries, the Indian subcontinent, and Japan.31–33 By definition,
the cause is unknown, but studies have found associations with other conditions
including immunologic disorders, genetic diseases, human immunodeficiency virus
infection, and exposure to drugs and toxins.29

Noninvasive diagnostic approaches such as liver imaging modalities are useful,
but the differential diagnosis to determine the cause of the portal hypertension
relies on thorough interpretation of the liver biopsy.34,35


CASE RESUMED: BIOPSY

The patient’s cirrhosis was presumed to be secondary to iron deposition. Results
of iron studies were as follows:

 * Ferritin level 1,227 µg/L (24–336)

 * Iron 156 µg/dL (50–150)

 * Total iron binding capacity 165 µg/dL (250–400)

 * Percent saturation > 90% (14%–50%).

However, the patient’s levels of liver enzymes and albumin were within normal
limits. We decided to confirm the diagnosis of cirrhosis and further investigate
its etiology with pathologic examination.

Transjugular liver biopsy was performed, and during the procedure the corrected
sinusoidal pressure gradient was 10 mm Hg, indicating sinusoidal portal
hypertension. Pathologic study of the sampled tissue revealed extramedullary
hematopoiesis, ie, production of blood cells outside of the bone marrow, and no
significant fibrosis on trichrome staining. The combination of portal
hypertension with patent portal and hepatic veins and no cirrhosis on liver
biopsy led to the diagnosis of noncirrhotic intrahepatic portal hypertension.


EXTRAMEDULLARY HEMATOPOIESIS

5. What are the organs most often affected by extramedullary hematopoiesis?

 * Liver and spleen

 * Kidney and adrenal glands

 * Lungs and pleura

 * Breasts

Patients with primary myelofibrosis can develop anemia and hepatosplenomegaly
due to ineffective erythropoiesis and extramedullary hematopoiesis.36

In extramedullary hematopoiesis, hematopoietic stem cells escape from the bone
marrow, travel through the bloodstream, and infiltrate other organs.37 In most
reported cases, the organs affected were the liver and spleen,38,39 but
extramedullary hematopoiesis can also affect the kidneys, adrenal glands, lymph
nodes, lungs, pleura, skin, breasts, dura mater, ovaries, thymus,
gastrointestinal tract, and central nervous system.37

In the liver, hematopoietic cells obstruct the sinusoids, resulting in portal
hypertension.37,40 This can be managed by placing a transjugular portosystemic
shunt to alleviate the symptoms,36 especially in patients presenting with
recurrent variceal bleeding and refractory ascites.2


FURTHER MANAGEMENT AND OUTCOME

On portal pressure measurement, the corrected sinusoidal gradient was a mean of
10 mm Hg, indicating sinusoidal portal hypertension. Portal hypertension has
been described in patients with myelofibrosis. The cause is not clear, but it
has been postulated that this is due to liver infiltration from extramedullary
hematopoiesis and fibrosis.

Therefore, the hematology care team decided to perform allogeneic stem cell
transplant. On post-transplant day 12, the patient’s course was complicated by
cytokine release syndrome, frequent diarrhea, hyperbilirubinemia with interval
development of ascites, and stress cardiomyopathy. He was admitted to the
intensive care unit for management of septic shock secondary to candidemia and
Candida krusei peritonitis. Sepsis was further complicated by acute hypoxic
respiratory failure, acute kidney injury, severe pulmonary edema, and episodes
of pulseless electrical activity. After a conversation with the family, the
patient was taken off life-support and pronounced dead.


TAKE-HOME POINTS

 * All patients with gastrointestinal bleeding should be thoroughly evaluated.

 * The Glasgow-Blatchford score is a useful tool to assess the need for
   hospitalization in patients with gastrointestinal bleeding.

 * In a patient with esophageal varices and no history of liver disease,
   noncirrhotic causes of portal hypertension should be considered.

 * Secondary prophylaxis after esophageal variceal bleeding is important to
   improve outcomes and reduce mortality.


DISCLOSURES

The authors report no relevant financial relationships which, in the context of
their contributions, could be perceived as a potential conflict of interest.

 * Copyright © 2022 The Cleveland Clinic Foundation. All Rights Reserved.




REFERENCES

 1.  ↵
      1. Mesa RA,
      2. Silverstein MN,
      3. Jacobsen SJ,
      4. Wollan PC,
      5. Tefferi A
     
     . Population-based incidence and survival figures in essential
     thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study,
     1976–1995. Am J Hematol 1999; 61(1):10–15.
     doi:10.1002/(sici)1096-8652(199905)61:1<10::aid-ajh3>3.0.co;2-i
     OpenUrlCrossRefPubMedGoogle Scholar
 2.  ↵
      1. Tefferi A
     
     . Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and
     management. Am J Hematol 2021; 96(1): 145–162. doi:10.1002/ajh.26050
     OpenUrlCrossRefPubMedGoogle Scholar
 3.  ↵
      1. Arber DA,
      2. Orazi A,
      3. Hasserjian R, et al
     
     . The 2016 revision to the World Health Organization classification of
     myeloid neoplasms and acute leukemia. Blood 2016; 127(20):2391–2405.
     doi:10.1182/blood-2016-03-643544
     OpenUrlAbstract/FREE Full TextGoogle Scholar
 4.  ↵
      1. Cervantes F,
      2. Dupriez B,
      3. Passamonti F, et al
     
     . Improving survival trends in primary myelofibrosis: an international
     study. J Clin Oncol 2012; 30(24):2981–2987. doi:10.1200/JCO.2012.42.0240
     OpenUrlAbstract/FREE Full TextGoogle Scholar
 5.  ↵
      1. Barkun AN,
      2. Almadi M,
      3. Kuipers EJ, et al
     
     . Management of nonvariceal upper gastrointestinal bleeding: guideline
     recommendations from the International Consensus Group. Ann Intern Med
     2019; 171(11):805–822. doi:10.7326/M19-1795
     OpenUrlCrossRefPubMedGoogle Scholar
 6.  ↵
      1. Blatchford O,
      2. Murray WR,
      3. Blatchford M
     
     . A risk score to predict need for treatment for upper-gastrointestinal
     haemorrhage. Lancet 2000; 356(9238):1318–1321.
     doi:10.1016/S0140-6736(00)02816-6
     OpenUrlCrossRefPubMedGoogle Scholar
 7.  ↵
      1. Oakland K
     
     . Risk stratification in upper and upper and lower GI bleeding: which
     scores should we use? Best Pract Res Clin Gastroenterol 2019; 42–43:101613.
     doi:10.1016/j.bpg.2019.04.006
     OpenUrlCrossRefGoogle Scholar
 8.  ↵
      1. Rockall TA,
      2. Logan RF,
      3. Devlin HB,
      4. Northfield TC
     
     . Selection of patients for early discharge or outpatient care after acute
     upper gastrointestinal haemorrhage. National Audit of Acute Upper
     Gastrointestinal Haemorrhage. Lancet 1996; 347(9009):1138–1140.
     doi:10.1016/s0140-6736(96)90607-8
     OpenUrlCrossRefPubMedGoogle Scholar
 9.  ↵
      1. Ramaekers R,
      2. Mukarram M,
      3. Smith CA,
      4. Thiruganasambandamoorthy V
     
     . The predictive value of preendoscopic risk scores to predict adverse
     outcomes in emergency department patients with upper gastrointestinal
     bleeding: a systematic review. Acad Emerg Med 2016; 23(11):1218–1227.
     doi:10.1111/acem.13101
     OpenUrlCrossRefPubMedGoogle Scholar
 10. ↵
      1. Stanley AJ,
      2. Laine L
     
     . Management of acute upper gastrointestinal bleeding. BMJ 2019; 364:l536.
     doi:10.1136/bmj.l536
     OpenUrlAbstract/FREE Full TextGoogle Scholar
 11. ↵
      1. Chandnani S,
      2. Rathi P,
      3. Udgirkar SS,
      4. Sonthalia N,
      5. Contractor Q,
      6. Jain S
     
     . Clinical utility of risk scores in variceal bleeding. Arq Gastroenterol
     2019; 56(3):286–293. doi:10.1590/S0004-2803.201900000-54
     OpenUrlCrossRefGoogle Scholar
 12. ↵
      1. Duarte-Chang C,
      2. Beitia S,
      3. Adames E
     
     . Glasgow-Blatchford usefulness in patients with non variceal upper
     gastrointestinal bleeding with low and high risk of complications seen at
     the Emergency Department of Santo Tomas Hospital, 2015–2016. Rev
     Gastroenterol Peru 2019; 39(2):105–110. Spanish. pmid:31333224
     OpenUrlPubMedGoogle Scholar
 13. ↵
      1. Talley N,
      2. Potter M
     
     . Glasgow Blatchford score predicted intervention or death better than 4
     other prediction models in upper GI bleeding. Ann Intern Med 2017;
     166(8):JC47. doi:10.7326/ACPJC-2017-166-8-047
     OpenUrlCrossRefGoogle Scholar
 14. ↵
      1. Cheng DW,
      2. Lu YW,
      3. Teller T,
      4. Sekhon HK,
      5. Wu BU
     
     . A modified Glasgow Blatchford Score improves risk stratification in upper
     gastrointestinal bleed: a prospective comparison of scoring systems.
     Aliment Pharmacol Ther 2012; 36(8):782–789. doi:10.1111/apt.12029
     OpenUrlCrossRefPubMedGoogle Scholar
 15. ↵
      1. Laine L,
      2. Cook D
     
     . Endoscopic ligation compared with sclerotherapy for treatment of
     esophageal variceal bleeding. A meta-analysis. Ann Intern Med 1995;
     123(4):280–287. doi:10.7326/0003-4819-123-4-199508150-00007
     OpenUrlCrossRefPubMedGoogle Scholar
 16. ↵
      1. Yoshida H,
      2. Mamada Y,
      3. Taniai N, et al
     
     . Risk factors for bleeding esophagogastric varices. J Nippon Med Sch 2013;
     80(4):252–259. doi:10.1272/jnms.80.252
     OpenUrlCrossRefGoogle Scholar
 17. ↵
      1. Wilbur K,
      2. Sidhu K
     
     . Beta blocker prophylaxis for patients with variceal hemorrhage. J Clin
     Gastroenterol 2005; 39(5):435–440. doi:10.1097/01.mcg.0000159222.16032.98
     OpenUrlCrossRefPubMedGoogle Scholar
 18. ↵
      1. Merkel C,
      2. Marin R,
      3. Angeli P, et al
     
     . A placebo-controlled clinical trial of nadolol in the prophylaxis of
     growth of small esophageal varices in cirrhosis. Gastroenterology 2004;
     127(2):476–484. doi:10.1053/j.gastro.2004.05.004
     OpenUrlCrossRefPubMedGoogle Scholar
 19. ↵
      1. World Gastroenterology Organisation
     
     . Esophageal varices.
     https://www.worldgastroenterology.org/guidelines/esophageal-varices/esophageal-varices-english.
     Accessed September 12, 2022.
     Google Scholar
 20. ↵
      1. Garcia-Tsao G,
      2. Abraldes JG,
      3. Berzigotti A,
      4. Bosch J
     
     . Portal hypertensive bleeding in cirrhosis: risk stratification,
     diagnosis, and management: 2016 practice guidance by the American
     Association for the study of liver diseases. Hepatology 2017;
     65(1):310–335. doi:10.1002/hep.28906
     OpenUrlCrossRefPubMedGoogle Scholar
 21. ↵
      1. Minoda AM,
      2. Cadete RBF,
      3. Teixeira SR,
      4. Muglia VF,
      5. Elias Junior J,
      6. de Melo-Leite AF
     
     . The ABCD of portal vein thrombosis: a systematic approach. Radiol Bras
     2020; 53(6):424–429. doi:10.1590/0100-3984.2019.0109
     OpenUrlCrossRefGoogle Scholar
 22. ↵
      1. Conejo I,
      2. Guardascione MA,
      3. Tandon P, et al
     
     . Multicenter external validation of risk stratification criteria for
     patients with variceal bleeding. Clin Gastroenterol Hepatol 2018;
     16(1):132–139.e8. doi:10.1016/j.cgh.2017.04.042
     OpenUrlCrossRefPubMedGoogle Scholar
 23.  1. García-Pagán JC,
      2. Caca K,
      3. Bureau C, et al
     
     . Early use of TIPS in patients with cirrhosis and variceal bleeding. N
     Engl J Med 2010; 362(25):2370–2379. doi:10.1056/NEJMoa0910102
     OpenUrlCrossRefPubMedGoogle Scholar
 24.  1. Khan S,
      2. Tudur Smith C,
      3. Williamson P,
      4. Sutton R
     
     . Portosystemic shunts versus endoscopic therapy for variceal rebleeding in
     patients with cirrhosis. Cochrane Database Syst Rev 2006; 2006(4):CD000553.
     doi:10.1002/14651858.CD000553.pub2
     OpenUrlCrossRefGoogle Scholar
 25. ↵
      1. Tan PC,
      2. Hou MC,
      3. Lin HC, et al
     
     . A randomized trial of endoscopic treatment of acute gastric variceal
     hemorrhage: N-butyl-2-cyanoacrylate injection versus band ligation.
     Hepatology 2006; 43(4): 690–697. doi:10.1002/hep.21145
     OpenUrlCrossRefPubMedGoogle Scholar
 26. ↵
      1. Guo H,
      2. Zhang F,
      3. Yin X, et al
     
     . Endoscopic therapy + beta-blocker vs covered transjugular intrahepatic
     portosystemic shunt for prevention of variceal rebleeding in cirrhotic
     patients with hepatic venous pressure gradient ≥ 16 mmHg. Eur J
     Gastroenterol Hepatol 2021; 33(11):1427–1435.
     doi:10.1097/MEG.0000000000001872
     OpenUrlCrossRefGoogle Scholar
 27. ↵
      1. Berzigotti A,
      2. Seijo S,
      3. Reverter E,
      4. Bosch J
     
     . Assessing portal hypertension in liver diseases. Expert Rev Gastroenterol
     Hepatol 2013; 7(2):141–155. doi:10.1586/egh.12.83
     OpenUrlCrossRefPubMedGoogle Scholar
 28. ↵
      1. Sarin SK,
      2. Philips CA,
      3. Khanna R
     
     . Noncirrhotic portal hypertension: medical and endoscopic management. Clin
     Liver Dis (Hoboken) 2015; 6(5):107–111. doi:10.1002/cld.511
     OpenUrlCrossRefGoogle Scholar
 29. ↵
      1. Fiel MI,
      2. Schiano TD
     
     . Idiopathic noncirrhotic portal hypertension. Semin Diagn Pathol 2019;
     36(6):395–403. doi:10.1053/j.semdp.2019.07.006
     OpenUrlCrossRefGoogle Scholar
 30. ↵
      1. Kleiner DE
     
     . Noncirrhotic portal hypertension: pathology and nomenclature. Clin Liver
     Dis (Hoboken) 2015; 5(5):123–126. doi:10.1002/cld.459
     OpenUrlCrossRefGoogle Scholar
 31. ↵
      1. Bodh V,
      2. Chawla Y
     
     . Noncirrhotic intrahepatic portal hypertension. Clin Liver Dis (Hoboken)
     2014; 3(6):129–132. doi:10.1002/cld.344
     OpenUrlCrossRefGoogle Scholar
 32.  1. Khanna R,
      2. Sarin SK
     
     . Non-cirrhotic portal hypertension—diagnosis and management. J Hepatol
     2014; 60(2):421–441. doi:10.1016/j.jhep.2013.08.013
     OpenUrlCrossRefPubMedGoogle Scholar
 33. ↵
      1. Khanna R,
      2. Sarin SK
     
     . Noncirrhotic portal hypertension: current and emerging perspectives. Clin
     Liver Dis 2019; 23(4):781–807. doi:10.1016/j.cld.2019.07.006
     OpenUrlCrossRefGoogle Scholar
 34. ↵
      1. Da BL,
      2. Koh C,
      3. Heller T
     
     . Noncirrhotic portal hypertension. Curr Opin Gastroenterol 2018;
     34(3):140–145. doi:10.1097/MOG.0000000000000433000433
     OpenUrlCrossRefGoogle Scholar
 35. ↵
      1. Riggio O,
      2. Gioia S,
      3. Pentassuglio I,
      4. Nicoletti V,
      5. Valente M,
      6. d’Amati G
     
     . Idiopathic noncirrhotic portal hypertension: current perspectives. Hepat
     Med 2016; 8:81–88. doi:10.2147/HMER.S85544
     OpenUrlCrossRefGoogle Scholar
 36. ↵
      1. Tefferi A
     
     . Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and
     management. Am J Hematol 2013; 88(2): 141–150. doi:10.1002/ajh.23384
     OpenUrlCrossRefPubMedGoogle Scholar
 37. ↵
      1. Kwak HS,
      2. Lee JM
     
     . CT findings of extramedullary hematopoiesis in the thorax, liver and
     kidneys, in a patient with idiopathic myelofibrosis. J Korean Med Sci 2000;
     15(4):460–462. doi:10.3346/jkms.2000.15.4.460
     OpenUrlCrossRefPubMedGoogle Scholar
 38. ↵
      1. Chiu SC,
      2. Liu HH,
      3. Chen CL, et al
     
     . Extramedullary hematopoiesis (EMH) in laboratory animals: offering an
     insight into stem cell research. Cell Transplant 2015; 24(3):349–366.
     doi:10.3727/096368915X686850
     OpenUrlCrossRefGoogle Scholar
 39. ↵
      1. Johns JL,
      2. Christopher MM
     
     . Extramedullary hematopoiesis: a new look at the underlying stem cell
     niche, theories of development, and occurrence in animals. Vet Pathol 2012;
     49(3):508–523. doi:10.1177/0300985811432344
     OpenUrlCrossRefPubMedGoogle Scholar
 40. ↵
      1. Yamamoto K,
      2. Miwa Y,
      3. Abe-Suzuki S, et al
     
     . Extramedullary hematopoiesis: elucidating the function of the
     hematopoietic stem cell niche (Review). Mol Med Rep 2016; 13(1):587–591.
     doi:10.3892/mmr.2015.4621
     OpenUrlCrossRefGoogle Scholar




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Cleveland Clinic Journal of Medicine
Vol. 89, Issue 10
1 Oct 2022
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A 65-year-old man with melena and a blood disorder
Monia E. Werlang, Marilia L. Montenegro, Bhaumik Brahmbhatt
Cleveland Clinic Journal of Medicine Oct 2022, 89 (10) 573-578; DOI:
10.3949/ccjm.89a.20175

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 * Article
    * PRIMARY MYELOFIBROSIS: A NEOPLASM OF BONE MARROW
    * CASE CONTINUED: INITIAL EVALUATION
    * DOES THE PATIENT NEED TO BE ADMITTED?
    * CASE CONTINUED: UPPER ENDOSCOPY PERFORMED
    * MANAGEMENT OF ESOPHAGEAL VARICES
    * CASE RESUMED: FURTHER INVESTIGATION
    * ETIOLOGY OF PORTAL HYPERTENSION
    * CASE RESUMED: BIOPSY
    * EXTRAMEDULLARY HEMATOPOIESIS
    * FURTHER MANAGEMENT AND OUTCOME
    * TAKE-HOME POINTS
    * DISCLOSURES
    * REFERENCES

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A 65-year-old man with melena and a blood disorder
Monia E. Werlang, Marilia L. Montenegro, Bhaumik Brahmbhatt
Cleveland Clinic Journal of Medicine Oct 2022, 89 (10) 573-578; DOI:
10.3949/ccjm.89a.20175


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