HAEMATOLOGY Flashcards
Classic Sickle cell findings
- Humeral head AVN
- H-type vertebra
- Autosplenectomy
- Interstitial pulmonary opacitites
Primary myelofibrosis
Dr Mostafa El-Feky◉ and Dr Yuranga Weerakkody◉ et al.
Primary myelofibrosis is a myeloproliferative neoplasm in which there is the replacement of bone marrow with collagenous connective tissue and progressive fibrosis. It is characterised by:
extramedullary haematopoiesis
progressive splenomegaly
anaemia
variable change in the number of granulocytes and platelets including thrombocytopenia
Epidemiology
It usually affects the middle-aged to elderly, with a mean age of 60 years 6. The estimated prevalence is ~1:100,000.
Pathology
It is considered a chronic BCR-ABL1 (breakpoint cluster region-Abelson murine leukaemia viral oncogene homologue 1)-negative myeloproliferative disorder 11.
Non-neoplastic fibroblasts produce collagen, which replaces normal bone marrow elements. This bone marrow fibrosis is a result of an inappropriate release of PDGF and TGF-ß from neoplastic megakaryocytes 8.
Radiographic features
Most radiological features are a result of extramedullary haematopoiesis and seen in many systems.
General
lymphadenopathy
Musculoskeletal
osteosclerosis
diffuse pattern
no bony architectural distortion
typical distribution:
axial skeleton
ribs
proximal humerus and femur
bone scan may give “superscan” appearance
Abdominal
hepatomegaly
splenomegaly: can be massive
some patients may also experience splenic infarcts 11
evidence of portal hypertension 3
from increased splenic blood flow
from portal flow obstruction from the sinusoidal haematopoietic proliferation
Cardiovascular
may show evidence of congestive cardiac failure due to anaemia 3
Treatment and prognosis
Prognosis is poor, with slow progression and death usually within 2-3 years. It can also transform into acute myeloid leukaemia in a small number of patients 10.
Complications
gout: from hyperuricaemia due to increased haematopoietic turnover
splenic rupture (rare) 9
bleeding from thrombocytopenia (see case 8)
Differential diagnosis
General differential considerations include:
for musculoskeletal manifestations: consider the differential diagnosis of diffuse bony sclerosis
for splenic manifestations: consider differential diagnosis for splenomegaly
See also
WHO classification of tumours of haematopoietic and lymphoid tissues
Splenomegaly
Dr Mohammad Osama Hussein Yonso◉ and Assoc Prof Frank Gaillard◉◈ et al.
Splenomegaly refers to enlargement of the spleen. The upper limit of normal adult splenic length is traditionally cited at 12 cm, but lengths upwards of 14 cm can be seen in normal, taller males 7.
Massive splenomegaly is variably defined, including when the spleen is 5 standard deviations above the mean normal volume (about 943 cm3) 4, heavier than 1000 g 5 or 1500 g 8, longer than 18 cm 8, or extending into the pelvis or across midline 4.
Pathology
The causes of splenomegaly are protean, and can be thought of under a number of headings 3,8:
haematological disease
haemodynamic
infectious
storage diseases/metabolic/infiltrative disorders
neoplastic (non-haematologic)
traumatic
connective tissue disorders
Haematological disease
anaemias
thalassaemia (including beta thalassaemia major*)
sickle cell disease with splenic sequestration (in young patients prior to developing autosplenectomy)
hereditary spherocytosis
pyruvate kinase deficiency
thrombotic thrombocytopenic purpura (TTP)
Plummer-Vinson syndrome
neoplastic/proliferative/redistribution of haematopoiesismyeloproliferative neoplasms*
chronic myeloid leukaemia
primary myelofibrosis
polycythaemia vera
essential thrombocytosis
chronic myelomonocytic leukaemia
acute leukaemia*
acute myeloid leukaemia
acute lymphoblastic leukaemia
lymphoma / chronic lymphoid neoplasms*
chronic lymphocytic leukaemia
Hodgkin lymphoma
non-Hodgkin lymphoma
hairy cell leukaemia
Waldenström macroglobulinaemia
extramedullary haematopoiesis
osteopetrosis
idiopathic hypereosinophilic syndrome
Haemodynamic
cirrhosis: portal hypertension (common)
congestive splenomegaly (Banti syndrome)
splenic vein obstruction
portal vein obstruction
right heart failure
cystic fibrosis 6
Infection
viral
EBV (infectious mononucleosis) (common)
AIDS with Mycobacterial avium complex infection*
CMV
herpes simplex virus
rubella
bacterial
tuberculosis (miliary)
tularaemia
subacute bacterial endocarditis
typhoid fever
brucellosis
syphilis
abscess
fungal
histoplasmosis (common)
candidiasis
parasitic disease
malaria* (hyperreactive malarial splenomegaly syndrome or tropical splenomegaly syndrome)
schistosomiasis
hydatid disease
leishmaniasis (kala-azar)*
rickettsial
typhus
Storage diseases/metabolic/infiltrative disorders
Gaucher disease*
glycogen storage disease
mucopolysaccharidoses
Niemann-Pick disease
haemochromatosis
amyloidosis
porphyria
sarcoidosis
Neoplastic (non-haematologic)
metastases (breast, lung, colon, ovary, melanoma)
haemangioma
lymphangioma
angiosarcoma
Trauma
haematoma
pseudocyst
Connective tissue disorders
rheumatoid arthritis
Felty syndrome
juvenile rheumatoid arthritis (JRA)
Still disease
systemic lupus erythematosus (SLE)
* may cause massive splenomegaly 3,8
Radiographic features
The shape and orientation of a spleen make accurate linear measurement difficult.
On CT, a splenic width measurement (largest anterior-posterior measurement on axial images) of greater than 10.5 cm is the most accurate single measurement for mild to moderate splenomegaly in patients with cirrhosis; while a craniocaudal measurement of greater than 14.6 cm is the most accurate single measurement for massive splenomegaly 4.
On sonographic assessment, a length of 12 cm is generally considered the upper limit of normal.
See also
spleen size (paediatric)
hepatosplenomegaly
fetal splenomegaly
fetal hepatosplenomegaly
can liver fibrosis in cirrhosis be reversed?
Robins:
Scar Formation and Regression (p. 823)
The hepatic stellate cell, a lipid (vitamin A) storing cell, is primarily responsible for liver scar deposition. Stellate cells can be activated by (1) inflammatory cytokines, such as tumor necrosis factor (TNF), lymphotoxin, and interleukin-1β (IL-1β), and lipid peroxidation products; (2) cytokine and chemokine production by Kupffer cells, endothelial cells, hepatocytes, and bile duct epithelial cells; (3) in response to disruption of the extracellular matrix (ECM); and (4) direct stimulation of stellate cells by toxins. Such activation causes stellate cells to develop into highly fibrogenic and contractile myofibroblasts; subsequent fibrogenesis is driven by cytokines released by Kupffer cells and lymphocytes (e.g., transforming growth factor-β [TGF-β]), and stellate cell contraction is stimulated by endothelin-1 (ET-1) (Fig. 18-1). Portal fibroblasts also contribute to scar deposition, with ductular reactions leading to the activation and recruitment of such fibrogenic cells.
FIGURE18-1
Stellate cell activation and liver fibrosis.
Kupffer cell activation leads to secretion of multiple cytokines. Platelet-derived growth factor (PDGF) and TNF activate stellate cells, and contraction of the activated stellate cells is stimulated by ET-1. Fibrosis is stimulated by TGF-β. Chemotaxis of activated stellate cells to areas of injury is promoted by PDGF and monocyte chemotactic protein-1 (MCP-1). See text for details.
If the chronic injury leading to scar formation is interrupted (e.g., clearance of hepatitis virus infection, cessation of alcohol use), then stellate cell activation ceases, and the fibrosis can be fragmented by metalloproteinases produced by hepatocytes. In this way, scar formation can be reversed.
https://gut.bmj.com/content/46/4/443
In summary, accumulating evidence suggests that liver fibrosis is reversible and that recovery from cirrhosis may be possible. Moreover, the application of cell and molecular techniques to models of reversible fibrosis are helping to establish the events and processes that are critical to recovery. It is anticipated that ultimately these approaches will lead to the development of effective antifibrotics, which harness or mimic the liver’s capacity for reversal of fibrosis with resolution to a normal architecture
Mortality rate of rupture oesophageal varicies
up to 50%
Path 2019 Aug q90
