Haematopoietic System

The haematopoietic system includes myeloid tissues (marrow and derived cells including RBC, platelets, granulocytes, monocytes) and lymphoid tissues (thymus, LN, spleen). The mononuclear phagocytes system (MPS, reticuloendothelial system) is the phagocytic cells (monocytes, macrophages) with accumulations in the LN, spleen, Kupffer cells of liver, tissue histiocytes, tonsils, adenoids, Peyer’s patches.

Embrylogically, haematopoietic stem cells (HSCs) migrate to the liver, then to the bone marrow before birth. Differentiation includes:

  • Multipotential myeloid progenitor -> committed precursors -> blast cells.
    • Proerythroblast -> erythrocytes
    • Megakaryoblast -> platelets
    • Myeloblast -> neutrophils
    • Monoblast -> monocytes
    • Eosinophiloblast -> eosinophils
    • Basophiloblast -> basophils
  • Multipotential lymphoid progenitor
    • T-cells
    • B-cells
    • Natural killer (NK) cells

Haematopoietic neoplasms may be lymphoid (B-cell, T-cell, NK), myeloid (AML, myelodysplastic syndromes, chronic myeloproliferative disorders), or histiocytoses (macrophages, dendritic cells including LCH). Generally the more undifferentiated the cell (close to pleuripotent), the larger the cell, more aggressive and more sensitive to therapy. The term leukemia is used for widespread involvement of bone marrow ± peripheral blood; lymphoma used for proliferations as discrete masses; but there is overlap.

The marrow cavity contains yellow/fatty marrow, red/haematopoietic marrow (intermediate T1 and T2) and trabecular bone (causes susceptibility). Red marrow may fill the entire cavity, have wispy ill-defined margins or occasionally rounded and well circumscribed masses. Conversion (red to yellow marrow) occurs 1st in epiphyses and apophyses within few months of ossification, terminal phalanges, distal -> proximal diaphyses -> metaphyses (starting early childhood), then flat bones; mostly complete by 25y with persisting red marrow in axial skeleton, proximal humeral and femoral metaphyses, occasionally humeral heads. Anything other than fat signal in an epiphysis or apophysis after 6/12 old is abnormal (except medial humeral head). Women may have spotty marrow in femurs and pelvis ?due to demands of menstruation. By 70s pedicles and posterior elements are converted to yellow marrow. Conversion is delayed/arrested in women, chronic anaemia, obesity, smoking, hypoxia. Reconversion (yellow->red) occurs with stress eg anaemia, heavy smoking, hypoventilation, hypoxia, decompensated heart disease, AIDS, ‘sports anaemia’ (endurance athletes), erythropoietin or granulocyte colony-stimulating factor; following in reverse order of original conversion.

Marrow infiltration usually causes T1 signal lower than muscle/disk, extensive marrow reconversion; or unusually high/low signal on fluid-sensitised sequences. Normal marrow shows signal loss on opposed phase of in-and-out of phase MRI, tumour doesn’t. Tc99m sulfur colloid is taken up by red marrow.

  • Myeloid depletion – Devoid of haematopoietic elements with signal same as fat on all sequences. From aplastic anaemia, radiation field, some chemotherapy agents.
  • Marrow oedema – Increased T2 from trauma, infection, transient osteoporosis, periphery of tumours. Might not reflect true oedema.
  • Haemosiderin deposition – From chronic haemolytic anaemia or transfusions, low signal on all sequences, also seen on liver and spleen.

Lymph nodes are bean-shaped with multiple afferent lymphatic channels entering the capsule, draining to subcapsular sinuses, with the efferent channel at the hilum (next to supplying artery and vein). The outer cortex contains lymphoid follicles (B-cells) separated by paracorticle zone (T-cells); inner medulla contains medullary sinuses, plasma cells, memory B-cells, T-cells, histiocytes. Primary follicles are round/oval unstimulated naive B-cells without a germinal centre. Secondary follicles develop after antigenic stimulation, consisting of inner germinal centre (activated B cells differentiating into plasma cells with helper T-cells); outer mantle zone (naive B-cells); and occasional surrounding marginal zone (B-cells with more cytoplasm than mantle B-cells). Lymphadenitis causes LN swelling and engorgement with large reactive germinal centres. The centre of follicles may undergo necrosis with pyogenic organisms, which may encompass the entire node.

Leukaemias cause hepatosplenomegaly, marrow infiltration, haemorrhage (low platelets), opportunistic infections, generalised osteoporosis, widened cranial sutures. Leukemic lines – lucent transverse metaphyseal bands abutting physis ?represent diminished mineralisation of endochondral ossification of new bone. Pronounced growth recovery lines from remissions and chemotherapy cycles.

Lymphoid Neoplasms

Most common adult primary mediastinal tumour. Calcification in untreated lymphoma is rare. Central necrosis in 20%. Low T1, high or intermixed low and high T2 (low representing fibrotic tissue in nodular sclerosing Hodgkin disease). Residual soft tissue after treatment in 50%, esp nodular sclerosing Hodgkin; may have recurrence in 6-12/12 best assessed with PET. Chronic immune stimulation may predispose to lymphoma, including H.pylori (gastric B-cell lymphoma), gluten-sensitive enteropathy (intestinal T-cell lymphoma), HIV/EBV/HepC (B-cell lymphomas).

WHO classifications of lymphomas divide into mature B-cell, mature T-cell, Hodgkin and immunodeficiency-associated lymphoproliferative disorders (as below).

Cotswald-modified Ann Arbor staging used for most lymphomas, with the exception of PCNS and primary cutaneous lymphomas (eg mycosis fungoides, Sezary syndrome) which use TNMB (tumour, LN, mets, blood); and Burkitt using St Jude.

  • Limited disease
    • Stage I – Single LN group or lymphoid organ (eg spleen, thymus). IE for extra-lymphoid organ (primary extranodal).
    • Stage II – >1 LN groups/lymphoid organs on one side of diaphragm
  • Advanced disease
    • Stage III – Both sides of the diaphragm involved. IIIS if spleen involved.
    • Stage IV – Non-contiguous extra-lymphatic organs/sites (eg liver, lung, marrow) ± lymphatic involvement.
  • Suffixes include:
    • A – asymptomatic; B – symptomatic (fever, night sweats, weight loss). Only used for HL (affects treatment).
    • E- primary extra-lymphatic organ or localised extra-lymphatic extension.
    • Bulky disease. For HL if a single nodal mass is >100mm maximal diameter (any plane) or >1/3 transthoracic diameter. Follicular >60mm and LBCL >60-100mm. Longest diameter recorded for staging, with X suffix no longer used.

PET is useful on initial diagnosis with increased sensitivity of disease when compared to CT alone (particularly extranodal sites) – potentially upstaging and changing treatment in approx 25-33% of patients. High FDG uptake (SUV>10) is suspicious for aggressive lymphoma. Pre-treatment splenic uptake more than liver indicates disease. Diffuse marrow uptake is nonspecific, can be response to cytokine stimulation (esp HL); focal uptake is more specific. Diffuse splenic and marrow uptake will also occur after haematopeietic stimulation agents. Monoclonal antibodies (eg retuximab) may cause a strong inflammatory flare. Deauville 5 point scale: 1 ≤ background, 2 ≤ mediastinum, 3 ≤ liver, 4 > liver, 5 markedly > liver or new lesions.  In DLBCL reduction in SUVmax by >2/3 after 2 cycles chemotherapy indicates satisfactory response (hence good prognosis).

Treatment is often based on the international prognostic index (IPI).

  • Most lymphomas (other than slow-growing follicular) – 1 point is given for each of: age>60, stage III-IV, >1 extra-lymphatic site, needs help with normal ADLs, elevated serum LDH. Risk groups include low (score 0-1), low-intermediate 2, high intermediate 3, high 4-5.
  • Revised IPI for fast-growing lymphoma who have had modern treatment – as above with risk groups very good 0, good 1-2, poor ≥3.
  • Follicular lymphoma IPI (FLIPI) – 1 point for each of: age>60, stage III-IV, Hb<120g/L, >4 LN groups, elevated serum LDH. Low risk 0-1, intermediate 2, high risk ≥3

Treatment aims for HL, aggressive NHL (eg DLBCL, peripheral T-cell) is cure. Indolent NHL usually incurable, treatment aim is to prolong survival.

Lugano classification used for standardised response assessment, particularly for clinical trials (previously IWG/Cheson). Eligible lesions are lymph nodes with longest transverse diameter >15mm, extranodal >10mm. Lesions measured longest transverse diameter and perpendicular short axis on the same slice, up to 6 lesions. The sum of the product of diameters (SPD) is calculated. Spleen measured in 3 perpendicular planes: longest transverse diameter, perpendicular short axis, and longest coronal vertical CC length (enlarged if >130mm). Response criteria:

  • CT
    • Complete response (CR) all nodal sites <15mm, and complete disappearances of other disease
    • Partial response (PR) ≥ 50% reduction in SPD
    • Stable <50% reduction SPD from baseline
    • Progressive disease new/increased node >15mm long axis + ≥50% product diameters from nadir + >5mm absolute increased diameter for <20mm lesions and >10mm for >20mm; or new/increased splenomegaly (with several rules), new/larger non-measured lesions, recurrent previously resolved lesions, new extranodal lesion >10mm, new node >15mm.
  • PET for FDG avid lymphoma (incl HL and DLBCL)
    • CR Deauville score 1-3 (with or without residual mass) at end of treatment. At interim/mid-treatment a score of 3 usually also CR, but some trials may be consider inadequate response.
    • PR score 4-5 with reduced uptake from baseline
    • Stable score 4-5 with no obvious change up uptake
    • Progressive score 4-5 with any lesion increased uptake from baseline or new FDG-avid site of disease

Non-Hodgkin Lymphoma (NHL, 60-80%)

Heterogeneous group of diseases with unpredictable involvement and variable prognosis, spreading early and wide. More common in AIDS and other immunocompromised. Intrathoracic disease in 40% with mediastinal nodes in 50% of these, abdominal adenopathy in 50%, spleen 40%, liver 15%. Extranodal sites are common (more common than HL), esp GI and urinary tract. Parenchymal involvement can occur in absence of LN involvement in 50% (cf HL). 50s. Types:

  • Mature/peripheral B-cell
    • Diffuse large B-cell lymphoma (DLBCL) – Most common NHL, mean 64yo. Large cells, diffuse pattern of growth, clinically aggressive with most advanced stage, typically high FDG uptake. Rapidly enlarging mass of nodes or extranodal, anywhere in body but commonly Waldeyer ring; other sites include GIT, skin, bone, brain. May be associated with oncogenic herpesvirus, T-cell immunodeficiency with EBV (HIV, allogenic bone marrow transplant).
    • Follicular lymphoma – Median age 60yo. Indolent, often asymptomatic. From germinal centre B cells. Usually diagnosed at advanced stange with diffuse adenopathy, common marrow involved. Variable FDG uptake.
    • Marginal zone lymphomas (MZL) – Median 65-70yo. 3 subtypes: LN (nodal marginal zone lymphoma, NMZL), spleen and extranodal mucosal-associated lymphoid tissue (MALToma). Extranodal tumours may arise in areas of chronic inflammation (eg salivary gland of Sjogren disease, thyroid gland of Hasimoto thyroiditis, stomach in H.pylori), may remain localised for prolonged periods and may regress after eradication of inciting agent. Variable FDG uptake.
      • Pulmonary lymphoma – From bronchus-associated lymphoid tissue (BALToma). May cause masses or airspace opacity (simulating pneumonia), coarse reticulonodular or tree-in bud uncommon, SPN rare.
    • Mantle cell lymphoma (MCL) – Median 68yo. Usually presents with stage IV disease, frequent GI and marrow. Leukemic phase in 75%, transformation to highly aggressive blastoid variant in 25%. Variable FDG uptake.
    • Burkitt lymphoma – African/endemic (latent EBV infection), sporadic/nonendemic or associated with HIV. All forms thought to be associated with EBV infection. High mitoses and apoptoses, starry sky histology (phagocytosed nuclear remnants in phagocytes with abundant clear cytoplasm). Endemic and sporadic usually children or young adults. Most are extranodal with endemic favouring mandible, abdominal viscera; sporadic ileocaecum and peritoneum.
    • Lymphoplasmacytic lymphoma – Typically 50s-60s. Most secrete monoclonal IgM (Waldenstrom macroglobulinaemia).
  • Mature/peripheral T cell and natural killer (NK) cell lymphomas – Including anaplastic large cell lymphoma. Extranodal NK/T-cell lymphoma infiltrates and surrounds small vessels leading to extensive ischaemic necrosis, esp nasopharyngeal; less commonly testis and skin.

Advanced or bulky disease usually treated with 6 cycles R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone) +/- RTx. Limited stage disease can be treated with 3-4 cycles cycles then RTx. Other options include ICE (ifosfamide, carboplatin, etoposide), R-EPOCH (rituximab, etoposide, prednisone, vincristine, doxorubicin).

Hodgkin Lymphoma (HL, 20-40%)

Giant multinucleated Reed-Sternberg cells (RS), make up >90% of the tumour cells, derived from the germinal centres. (RS cells also seen in infectious mononucleosis, solid cancers, large-cell NHLs). Bimodal peaks 25-30yo and 60-70yo. RS cells commonly infected with EBV. Involves thorax in 85%, most anterior mediastinal (esp nodular sclerosing type) or hilar LN enlargement. Cervical and supraclavicular lymphadenopathy in 80-90%, abdominal adenopathy in 25%, spleen in 40%, liver in 8%. More commonly localised to a single axial group of nodes (cf NHL in multiple groups of peripheral nodes), with orderly contiguous spread to adjacent nodal groups. High FDG uptake. Waldeyer ring is rarely involved (cf NHL). B symptoms in 25%, fever from inflammatory cytokines. Lung parenchymal involvement 2-3x more likely than NHL with linear and coarse reticulonodular opacity extending directly from LN, cause mass-like lesions and airspace shadowing. Atelectasis usually from obstructing endobronchial involvement, rarely from extrinsic compression. May -> subpleural lymphatics -> subpleural plaques/masses. Types include:

  • Classical Hodgkin Lymphoma (CHL)
    • Nodular sclerosing (most) – Large tumour nodules surrounded by bands of inflammatory cells and sclerosis.
    • Mixed cellularity – RS cells mixed with numerous inflammatory cells.
    • Lymphocyte rich – Rare, best prognosis.
    • Lymphocyte depletion – Rare, may be confused with large-cell NHL.
  • Lymphocyte predominant Hodgkin lymphoma – Reed-Sternberg cells have immunophenotype different from the classical types.

Curable in most. Most common treatment is ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) +/- consolidative RTx. Consolidative RTx may be consitered for initially bulky disease. Second-line chemo used for refractory (not responding to initial treatment) or relapsed disease, then if responds consolidative high dose therapy with autologous stem cell transplant.

Post-Transplantation Lymphoproliferative Disorder (PTLD)

Lymphoid hyperplasia/neoplasia in 20% of those with solid organ transplants and immunosuppressives. ?From EBV induced proliferation of B lymphocytes which may range from polyclonal benign to aggressive monoclonal lymphoma. Extranodal lesion(s) in organs most common, adenopathy may occur near transplanted organ or remote sites. Tx reduction of immunosuppressives.

Plasma Cell Neoplasms/Dyscrasias

Secrete monoclonal Ig or Ig fragment (M components) with excessive light or heavy chains (light chains in urine = Bence-Jones proteins).

  • Multiple myeloma (plasma cell myeloma) – Tumorous masses throughout the bones. May spread to LN and extranodal sites. Most commonly vertebrae, ribs, skull, femur, clavicle, scapula. Starts in medullary cavity and progressively destroy the cortex. Punched-out lesions. Impaired humoral immunity with higher risk of esp encapsulated organisms. Mean survival 3yrs. Elevated immunoglobulins on serum electrophoresis, serum light chains, Bence-Jones proteinuria.
  • Solitary myeloma (plasmacytoma) – Uncommon variant of MM with a mass in bone or soft tissue, similar locations as MM. Almost always progresses to MM, but may take 10-20yrs.
  • Other subtypes – Waldenstrom macroglobulinaemia (may be associated with lymphoplasmacytic lymphoma), heavy-chain disease, primary or immunocyte-associated amyloidosis, monoclonal gammopathy of undetermined significance (MGUS).

Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) – Most common cancer of children, most <15yo, whites>blacks, M>F. Marrow is hypercellular packed with lymphoblasts replacing normal marrow elements.

  • B-cell acute lymphoblastic leukaemia/lymphoma (B-ALL, 85%) – Precursor/immature B cells.
  • T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL) – Precursor/immature T-cell. Thymic mass in 50-70%, also more likely to have lymphadenopathy, splenomegaly.

Chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) – Most common leukemia in adults, median 70yo, M>F. Diffuse infiltration of LN with proliferation centres. Generalised small volume lymphadenopathy and hepatosplenomegaly in 50-60%. May transform into a diffuse large B-cell lymphoma (Richter syndrome) in 5-10% with rapidly enlarging mass within a LN or spleen. May be just monitored or treated with immunochemotherapy.

Myeloid Neoplasms

All originate from transformed haematopoietic progenitors, and tend to evolve to more aggressive forms (eg AML).

Acute Myeloid Leukaemia (AML)

Mutation leading to accumulation of immature myeloid blasts in the marrow. Risk increases with age.

Myelodysplastic Syndromes (MDS)

Clonal stem cell disorder leading to ineffective haematopoiesis causing cytopenia. Predominantly elderly. High risk of transformation to AML. Marrow partly or wholly replaced by the clonal progeny. Primary/idiopathic or secondary (drug, radiotherapy after 2-8yrs).

Myeloproliferative Disorders

Increased production of one or more blood cell types due to growth factor-independent proliferation. Late spent phases cause extensive marrow fibrosis with increasing extramedullary haematopoiesis. Reconversion in large tubular bones and extramedullary haematopoiesis (hepatosplenomegaly, paraspinous masses, lymphadenopathy). These reconverted sites may also become fibrotic.

  • Chronic myeloid luekaemia (CML) – Leukocytosis, marrow markedly hypercellular. Peak 40s-50s. Splenomegaly from extramedullary haematopoiesis with infarcts of varying ages.
  • Polycythaemia vera (PCV) – Panmyelosis with incread RBC, granulocytes, platelets. Marrow hypercellular but some residual fat. Mild organomegaly. Late spent phase with extensive marrow fibrosis with increasing extramedullar haematopoiesis.
  • Essential thrombocythaemia (ET) – Marrow cellularity only mildly increased.
  • Primary myelofibrosis – Deposition of collagen by non-neoplastic fibroblasts. Fibrosis in regions usually involved in haematopoiesis with extensive extramedullary haematopoiesis esp spleen. Symmetric sclerotic trabeculae causing diffuse/patchy increased density, cortical thickening in vertebrae, pelvis, ribs, long tubular bones without expansion, low T1 and T2.
  • Systemic mastocytosis – Rare proliferation of mast cells, may be limited to skin (urticaria pigmentosa) or systemic. Marrow infiltration with mast cells, histamine release -> osteoporosis, lytic lesions, focal/generalised sclerosis or mixed patterns.
  • Chronic eosinophilic leukaemia
  • Stem cell leukaemia

Langerhans Cell Histiocytosis (LCH)

Histiocytosis is a group of proliferative disroders of dendritic cells or macrophages; may be benign/reactive or malignant, with LCH being intermediate. Langerhans cells are immature dendritic cells, LCH monoclonal proliferation. Vacuolated cytoplasm with Birbeck granules. Clinicopathological syndromes include:

  • Multifocal multisystem LCH (Letterer-Siwe disease) – Most <2yo, but may affect adults. Cutaneous lesions, hepatosplenomegaly, lymphadenopathy, pulmonary lesions, later destructive osteolytic lesions. More anaplastic tumours are Langerhans cell sarcomas.
  • Unifocal and multifocal unisystem LCH (eosinophilic granuloma) – Langerhans cells mixed with other inflammatory cells. Typically medullary cavity of bones (esp skull, ribs, femur), less commonly skin, lungs, stomach.

Erythrocyte and Bleeding Disorders


Microcytic hypochromic usually disorders of haemoglomin synthesis (esp iron deficiency). Macrocytic often impaired maturation in the bone marrow. Normochromic normocytic are nonsepcific. Pale, weak. Hypoxia may cause fatty change in the liver, myocardium and kidney. Causes include:

  • Blood loss – Acute (trauma) or chronic (GIT, gynaecological).
  • Haemolytic anaemias – Premature destruction with RBC life span <120 days, elevated erythropoetin, acumulation of haemoglobin degradation products (unconjugated bilirubinaemia). Extravascular haemolysis (most) – from phagocytosis due to alterations in the RBC making it less deformable; causing reactive phagocyte hyperplasia and splenomegaly. Intravascular haemolysis from mechanical injury, complement, intracellular parasites, exogenous toxins.
    • Hereditary spherocytosis – RBC membrane defect.
    • Sickle cell disease (HbS) – AR, 1% of African Americans. Chronic haemolytic anaemia and microvascular occlusion, marow hyperplasia, extramedullary haematopoiesis, marrow reconversion. Renal papillary necrosis, cholelithiasis (RBC lysis with bilirubinate stones), splenic autoinfarction (autosplenectomy from trapping of RBC in cords and sinuses; splenomegaly in less severe sickle cell trait), cardiomegaly, stroke, pulmonary infarction. Dactylitis (hand-foot syndrome) in 10-20%, cold -> vasoconstriction in persistent haematopoietic marrow of digits -> periostitis and soft tissue swelling. AVN of femoral and humeral heads. Bone marrow infarcts with patchy/serpiginous sclerosis, occasionally periostitis, marrow oedema with minimal enhancement, but intense periosteal enhancementand oedema. Central vertebral body collapse with H-shaped vertebrae (sickle cells form sludge in looping arcades of endplates). Diffuse increased bone scan uptake with focal uptake in healing infarcts. Prone to osteomyelitis (esp Salmonella, but Staph still more common).
    • Glucose-6-Phosphae dehydrogenase (G6PD) deficiency – Prone to oxidants with intravascular and extravascular haemolysis.
    • Thalassaemia – RBC prone to destruction.
    • Microangiopathic haemoloytic anaemias and DIC – Microvascular luminal narrowing ± fibrin and platelet deposition inducing shear stresses on passing RBC. Includes disseminated intravascular coagulation (DIC), thrombotic thrombocytopaenia purpura (TTP), haemolytic-uraemic syndrome (HUS), malignant HTN, SLE, disseminated cancer.
    • Mechanical injury – Cardiac valves, thrombotic narrowing of the microcirculation, bongo drumming, marathon, karate chopping.
    • Haemolytic disease of the newborn – Rhesus incompatibility.
    • Transfusion reactions
    • Infection – Malaria.
    • Hypersplenism – Increased RBC sequestration.
  • Reduced erythropoiesis
  • Megaloblastic anaemias
    • B12 deficiency – B12 (cobalamin) binds to intrinsic factor (secreted by parietal cells of fundus) and absorbed by the ileum. Deficiency in malabsorption, intrinsic factor deficiency (pernicious anaemia or gastrectomy), diffuse intestinal disease, ileitis, ileal resection. Pernicious anaemia is autoimmunity against gastric mucosa causing chronic atrophic gastritis (esp parietal cells of fundus), atrophic glossitis (shiny beefy tongue). CNS demyelination of dorsal and lateral tracts of spinal cord.
    • Folate deficiency – Decreased intake (malabsorption, alcoholism), increased requirements (pregnancy, infancy, haemolytic anaemias, disseminated cancer), folic acid antagonists (methotrexate), haemodialysis.
  • Thalassaemia – AR, common in Mediterranean, African Americans. Impaired α or β globin of haemoglobin with reduced production and RBC prone to destruction. β thalassemia major (Cooley’s anaemia, homogeneous) has poor prognosis with early childhood death, more severe radiographic findings. Marrow hyperplasia with expanded marrow space, squaring of metaphyses, osteopenia. Widened cranial diploic space inducing new bone formation (hair-on-end, crew-cut), obliteration of paranasal sinuses, hypertelorism, altered dentition. Erlenmeyer flask deformity in distal femurs. Multiple transfusions -> haemochromatosis ± CPPD and haemosiderosis. β-thalassaemia minor/trait is heterogeneous.
  • Iron deficiency anaemia
  • Erythropoietin deficiency – Renal failure, anaemia of chronic disease.
  • Aplastic anaemia – Pancytopaenia; from idiopathic, toxins, whole body radiotherapy, viruses, Fanconi anaemia (AR, faulty DNA repair). No splenomegaly.

Bleeding Diatheses

Causes include:

  • Fragility of vessels (nonthrombocytopaenic purpuras) – Infections (vasculitis, DIC), drug reactions, scurvy, Ehlers-Danlos syndrome, Cushing syndrome, Henoch-Shconlein purpura, hereditary haemorrhagic telangiectasia, perivascular amyloidosis.
  • Thrombocytopaenia – Reduced production (aplastic anaemia, leukaemia etc), reduced platelet survival (DIC, ITP, drugs eg heparin), sequestration (splenomegaly), dilution (transfusion).
    • Immune thrombocytopaenic purpura (ITP) – Autoantibodies to platelets. Spleen normal size, but congested sinusoids and enlarged splenic follicles. Diagnosis of exclusion.
    • Thrombotic microangiopathies – Thrombotic thrombocytopaenic purpura (TTP) and haemolytic-uraemic syndrome (HUS), excessive activation of platelets with microcirculatory deposits. Laboratory coagulation tests are usually normal.
    • Disseminated intravascular coagulation (DIC) – Acute, subacute or chronic thrombohaemorrhagic disorder with excessive activation of coagulation, microvascular thromboses. Consumption of platelets, fibrin and coagulation factors causing abnormal coagulation tests. Secondary to obstetric complications (placental/foetal material or amniotic fluid in circulation), malignant neoplasms, sepsis, major trauma/surgery/burns. May cause ischaemia of affected/vulnerable organs (eg Waterhouse-Friderichsen syndrome of adrenals, Sheehan post-partum pituitary necrosis) and/or haemorrhagic diathesis.
  • Defective platelet function – Rare, inherited.
  • Deranged coagulation
    • Von Willebrand Disease – Reduced vWF produced by endothelial cells (and megakaryocytes) which promotes adhesion of platelets and stabilises factor VIII.
    • Haemophilia – Type A (Factor VIII deficiency) and B (Factor IX deficiency, Christmas disease) – Both X-linked recessive. Easy bruising, massive haemorrhage after trauma/surgery, spontaneous haemorrhages.
      • Haemarthroses, may be from trivial trauma. Knee (wide intercondylar notch), elbow (large radial head, wide trochear notch), ankle, less commonly hip, shoulder. Multiple episodes -> synovial hypertrophy with haemosiderin deposits (dense on XR, low T1, intermediate/low T2, blooming on gradient), hyperaemia (periarticular osteopenia, metaphyseal flaring and epiphyseal overgrowth, gracile diaphyses, early physeal fusion), articular cartilage destruction, erosions, subarticular cysts, secondary OA. DDx JRA (usually unilateral), PVNS.
      • Pseudotumour of haemophilia – Intraosseous, subperiosteal or soft tissue repetitive bleeding -> internal/external scalloping, pressure erosions, periosteal reaction (usually sclerotic margins), large soft tissue mass with blood products of varying age (bizzare MRI signal), may have low signal fibrous/haemosiderin rim. Esp femur, pelvis, tibia, calcaneus.


Johnson SA1, Kumar A1, Matasar MJ1, Schöder H1, Rademaker J1. Imaging for Staging and Response Assessment in Lymphoma. Radiology. 2015 Aug;276(2):323-38. PMID: 26203705. [PubMed] [Read by QxMD]