Why Blood Loss From Sites other than Gastrointestinal Tract Rarely Causes Iron Deficiency?


A 55 year old man presented with breathlessness on climbing stairs. He saw his family physician who found the patient to be pale. The patient was advised a complete haemogram. He was found to be anaemic and was asked to see a haematologist.

The haemogram showed an haemoglobin of 3.1 g/dL with an MCV of 63fl. The WBC count was 5600 with 65% neutrophils, 30% lymphocyte, 3% monocytes and 2% eosinophils. The platelet count was 475 X 1009/L. The reticulocyte count was 1%.

The serum iron was 15μg/dL and the total iron binding capacity 450μg/dL and a transferrin saturation of 3.3%. The serum ferritin was 8ng/ml. A diagnosis of iron deficiency anaemia was made he was initiated on oral iron which he responded to. 

Iron deficiency is common in 

  1. Growing children because of dietary deficiency
  2. Women in the reproductive age group because of menstrual blood losses and iron depletion because of foetal transfer of iron during pregnancy.

When iron deficiency occurs in a well nourished man or a well nourished post-menopausal women it is invariably due to a gstrointestinal blood loss. Why is gastrointestinal blood loss different from other forms of blood loss?

Bleeding is an alarming symptom. It is rare for a person to ignore bleeding. Bleeding from the respiratory system, urinary system and skin is apparent and alarming. Such bleeding prompts the patient to promptly seek medical attention. Gastrointestinal bleeding may be of three types. The patient may pass fresh blood, the patient may have malaena or the patient may have occult bleeding. Passage of fresh blood with stools is a symptom of a lower gastrointestinal pathology. Such patients seek attention early and usually do not become anaemia. Haemorrhoids is an exception not because the patient does not realise that there is bleeding but because the patient may ignore the bleeding because he/she attributed it to a known cause. Some patients may not realise the significance of malaena and may present only when anaemic. A patient may loose upto  30ml of blood without a change in the consistency or colour of stools. Such patients present with iron deficiency anaemia. As the anaemia has a gradual onset the it may become severe and yet not cause symptoms. 

The diagnosis of anaemia is complete only if the type of anaemia and the cause of anaemia are determined. A rule of thumb is that unexplained iron deficiency anaemia in a man or a postmenopausal woman should be considered to be due to a occult gastrointestinal blood loss unless proven otherwise. The importance of this practice can not be overemphasised. A colon cancer develops in an adenoma. Completing the evaluation of an iron deficency anaemia provides an opportunity to diagnose a colorectal cancer either in the premalignment stage or when the disease has a limited extent. Not perusing the diagnostic evaluation of an iron deficiency anaemia to completion may close the window of early diagnosis of gastrointestinal cancer.

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Classification of β-Thalassaemia


β-Thalassaemia is a term applied to describe heterozygous group of diseases that are characterised by a decrease in the production of β globin  chain. Over 200 mutations in the β-globin gene and promoter regions that cause β-thalassaemia have been recognised. Thalassaemic alleles that produce no β-chain are designated β0 and those producing some β chain are designated as β+.  Before the genetic basis of thalassaemia was understood the disease was classified according to the clinical presentation and natural history of the disease. The genetic defects need to be determined for prenatal diagnosis but the clinical patterns remains relevant for clinical management of β-thalassaemia.

Based of the severity of disease three patterns of disease have been identified, thalassaemia major, thalassaemia minor and thalassaemias intermedia

  1. Thalassaemia Major: Thalasaemia major is a transfusion dependent anaemia that usually appears early in life, often in the first year. Anaemia is associated with splenomegaly, skeletal deformities and growth retardation. Iron overload develops by the end of second decade unless chelation is used. Unless treated with blood transfusion and chelation or allogeneic stem cell transplant, it is a fatal illness. There is a severe impairment of β-chain synthesis. Genetically these patients may be β0β0, β0β+ or β+β+.
  2. Thalassaemia Minor: patients with thalassaemia minor are asymptomatic. They are diagnosed when a complete haemogram is performed as a part of antenatal care or as a pert of investigations of another illness. Genetically they me be β0β or β+β.
  3. Thalassaemia Intermedia: Thalassaemia intermedia has a clinical presentation between that of thalassaemia major and thalassaemia minor. It is a very heterogeneous condition. The patient is not transfusion dependent but anaemic with a low and stable haemoglobin. Transfusion may be needed during periods of stress like infection and pregnancy. Advancing age is also associated with transfusion requirement. This may in part be due to hyperplenism associated with splenomegaly. The genetics of thalassaemia intermedia are complex. It may result from a mild β chain defect or because of interaction of β chain defects with other defects of haemoglobin synthesis

Manifestations of Lymphoma


Lymphomas are the most prevalent haematological malignancies. They are highly curable particularly in the early stage. As is the case with all cancers, there are no symptoms typical of lymphoma. The manifestations of lymphoma include:

Lymphadenopathy

Lymph node may be classified into superficial or deep group.

  1. Superficial Nodes: Superficial nodes include occupital, cervical, supraclavicular, epitrochlear, axillary, inguinal node.
    1. Cervical Nodes: Enlargement of cervical nodes is common. Children may have palpable cervical nodes that regress with age. These nodes are usually soft and small. Large, firm to hard, matted or enlarging cervical nodes need evaluation. The commonest cause of enlargement of cervical nodes is infection of upper repiratory tract. Patients with cervical lymphadenopathy associated with an upper respiratory tract infection need to be followed up till the lymph node regress. Nodes that do not regress after the infection subsides need evaluation.
    2. Occipital Nodes: Occipital nodes may be enlarged in patients with lice infestations. It is unusual to find occipital node engagement in disease.
    3. Axillary Nodes: Enlargement of axillary nodes usually indicates a disease in the draining areas – upper limbs, breast, lungs. Patients with recurrent trauma of the upper limbs may have enlarged axillary nodes.
    4. Inguinal Nodes: Inguinal lymphadenopathy is a feature of disease of the lower limb and the anogenital region. Recurrent trauma to the lower limbs can cause inguinal lymphadenopathy.
    5. Epitrochlear Nodes: Enlarged epitrochlear or popleteal nodes always indicates a disease, usually one causing a diffuse lymphadenopathy.
  2. Deep Nodes: The deep nodes include the mediastinal, hilar, intra-abdominal and pelvic nodes. Enlargement of these nodes causes pressure symptoms and is . Enlargement of  these nodes indicates disease.

Almost all Hodgkin’s lymphomas and majority of non-Hodgkin’s lymphoma present with enlargement of lymph nodes. Lymphadenopathy is a common symptom. It may be a result of  infection, inflammation or malignancy.

  1. Lymphadenopathy of Acute Infection/Inflammation: Patients with acute inflammation can be differentiated from lymphoma as they have painful and tender nodes often with erythema of the overlying skin. These node can suppurate. The area drained by the node has a inflammatory lesion, usually an infection.
  2. Lymphadenopathy of Chronic Infection/Inflammation: Lymphadenopathy of chronic inflammation has lacks erythema, pain and do not suppurate. The node enlarge at a slower rate. Differentiation of lymphadenopathy caused by chronic inflammatory disorders and malignancy can only be made by pathological examination of the nodes. The differentiation between tuberculous lymphadenitis and lymphoma (particularly Hodgkin’s lymphoma) can be challenging as regions of the world that have high prevalence of tuberculosis also have a resource constrain.

 

Tuberculosis lymphadenitis is common in resource constrained regions of the world. It is the practice in these regions to initiate anti-tuberculous therapy for patients with matted cervical nodes either on clinical grounds or following a fine needle aspiration cytology. While this can not be justified scientifically, proponents of this practice point to the lack of healthcare infrastructure to justify this practice. If one is choosing this path one must follow the patient to confirm regression and be aware of the existence of paradoxical response in tuberculosis. Paradoxical response is characterised by increase in constitutional symptoms and lymph node size on initiation of anti-tuberculous treatment. It is seen in about 10-15% patients.

Splenomegaly and Hepatomegaly

Spleen is a lymphoid organ. Lymphomas can originate in the spleen of the spleen can be secondarily involved by lymphoma. Primary splenic lymphomas, defined as splenic involvement without lymph node involvement forms about 6% of all lymphomas (Blood 2010; 117:2585). The symptoms of splenic lymphomas include abdominal discomfort and early satiety due to splenomegaly, constitutional symptoms like fever, weight loss and night sweats due to underlying lymphomatous process.  Patients with splenic lymphomas may have alterations in blood counts. Important history includes that of infections hepatitis C, hepatitis B, autoimmune disorders, treatment with anti-TNF agents.

Bone Marrow and Peripheral Blood

All lymphomas may involve the bone marrow and spread into the blood. Bone marrow and peripheral involvement is common in two groups of lymphoma the very high grade lymphomas like lymphoblastic lymphoma and Burkitt’s lymphoma and low grade lymphomas like small lymphocytic lymphoma. Bone marrow involvement in lymphoblastic lymphoma and Burkitt’s lymphoma manifests as acute lymphoblastic leukaemia is destructive. It manifests as leucocytosis and bone marrow failure (anaemia, neutropenia, thrombocytopenia). Leucocytosis is also a feature of bone marrow involvement with low grade lymphomas. These cells are mature. The growth is accommodative and cytopenias occurs late in the disease, if at all.

Extranodal Lymphomas

It is exceptional to have an extra-nodal Hodgkin’s lymphoma. The proportion of extra nodal non-Hodgkin lymphoma varies across the world.

  1. Gastrointestinal Tract: The commonest site of extranodal involvement is the gastrointestinal tract. Within the gastrointestinal tract, stomach is the commonest site for extranodal lymphomas of the gastrointestinal tract followed by small intestine, colon and oesophagus. The most common manifestation of gastrointestinal lymphoma is nonspecific symptoms like abdominal dyscomfort and pain. Anaemia is a feature of gastric and colonic lymphoma. High grade small intestinal lymphoma may present with intussusception.
  2. Skin Involvement: Cutaneous lymphomas are a distinct entity. Unlike other sites many cutaneous lymphomas are of T cell origin. They present with macules, papules and nodules.
  3. Central Nervous System: Central nervous system may manifest with global symptoms like comfusion, headache and altered consciousness, may have foaly neurolohical deficiit, seizures or multiple cranial nerve involvement because lymphomatous meningitis
  4. Primary testicular lymphoma presents as a unilateral painless swelling of the testis in an elderly male (see Primary Testicular Lymphoma). Hydrocele is present in about 40% of the patients.

Presentation Peculiar to Some Lymphomas

  1. Lymphoplasmacytic lymphoma is unlike other lymphomas in that symptoms of fatigue, weakness and breathlessness dominate. Splenomegaly and lymphoadenopathy are uncommon. Patinets may develop symptoms of hyper viscosity including headache, blurring, eipstasix.
  2. Nasal NK/T cell lymphoma presents with obstructive and destructive mass in the upper aerodigestive tract. It is reported most commonly in patients from the far east.
  3. Hepatosplenic γδ-T cell lymphoma presents with hepatosplenomegaly, no adenopathy, B symptoms and cytopenias. Patinets may have history of anti-TNF therapy for Crohn’s disease.
  4. Intravascular diffuse Large B Cell lymphoma is characterized by disseminated intravascular proliferations of B cells most commonly in the vessels of the CNS, kidney and lungs. Patinets present with symptoms secondary to vascular occlusion. The diagnosis is usually difficult.

Paraneoplastic Syndromes

Paraneoplastic syndromes associated with lymphomas include hypercalcaemia, syndrome of inappropriate ADH secretion, paraneoplastic ceribellar degeneration, motor neuron disease, acute polyradiculopathy, polyneuropathy of paraproteinaemia, neuropathy due to paraneoplastic vasculitis, neuromuscular junction disorders, sweets syndrome and minimal change nephrotic syndrome (see paraneoplastic syndromes associated with lymphoma for more conditions and a detailed discussion).

Evaluation of a Bleeding Patinet


From the point of evaluation of a bleeding patients haemostasis can be divided into the following parts.

  1. Platelets,
  2. Vessel wall
  3. Coagulation system: The coagulation system has the three parts intrinsic pathway, extrinsic pathway and common pathway.  The framework of intrinsic pathway, extrinsic pathway and common pathway are useful to understand how to interpret coagulation tests but does not reflect how coagulation proceeds in vivo.
    1. Intrinsic pathway: Coagulation by the intrinsic pathway starts by contact activation of factor XII, this in turn sequentially activates factors XI and IX. Activated factor XI with its cofactor activated factor VIII lyse and activate factor Xa. Factor XII has no role in coagulation in vivo.
    2. Extrinsic pathway: Coagulation by the extrinsic pathway involves activation of factor VII by tissue factor.  Activated factor VII then activates factor X.
    3. Common Pathway: Common pathway includes factor X, its cofactor factor V, prothrombin and thrombin
  4. Thrombolytic system.

The first step in the evaluation of a patients with a bleeding tendency is to perform screening tests to determine which part of the clotting system  is involved. This can be done with the use of the following tests.

  1. Prothrombin time: Prothrombin time asses the efficiency of extrinsic coagulation pathway.
  2. Activated Partial Thromboplastin Time: Activate partial Thromboplastin time assess the efficiency of intrinsic coagulation pathway
  3. Thrombin Time: Thrombin time asses the amount and quality of fibrin.
  4. Platelet Counts

The results of first-line tests are interpreted as follows.

    1. All tests deranged (Prolonged PT, APTT and TT and Low platelets): Derangement of all screening tests for coagulation is seen in patients with disseminated intravascular coagulation, coagulopathy of chronic liver disease, and acute live cell failure. Patients who have received a massive transfusion may also show this pattern of first line tests. In addition to there being a history of massive transfusion, these patients do not show increase in fibrin degradation products (D-dimer).
    2. Global coagulation defect with normal platelet counts (prolonged PT, prolonged APTT, prolonged PT normal platelets): All three first-line tests are abnormal in patients with primary fibrinogenolysis, fibrinogen deficiency, dysfibrinogenaemia, liver disease or treatment with conventional heparin.
    3. Global coagulation defect with normal fibrinogen and platelets (Prolonged PT and APTT normal TT and Platelets):
      1. Fibrinogen synthesis is not vitamin K dependent. Lack of vitamin K coenzyme activity, as is seen in vitamin K deficiency or use of warfarin like anticoagulants, affects the factors of the intrinsic system (factor II and IX ) and extrinsic system (factor VII). The PT and APTT prolong but TT which depends only on fibrinogen remains normal.
      2. The components of the common pathway include factor V, X and factor II. Deficiency of these factors or the presence of inhibitors against any of these factors causes prolongation of PT and APTT but a normal TT.  A rare autosomal recessive disorder, combined factor V and VIII deficiency can cause prolongation of PT and APTT with a normal TT.
      3. Some patients with liver disease may have a prolonged PT and TT.
    4. Isolated prolongation of APTT (Normal PT, Prolonged APTT, Normal TT, Normal Platelets counts): The commonest cause of isolated prolongation of APTT is deficiency or inhibitors of factor VIII or factor IX. Deficiency of other components of the intrinsic pathway including factors XI and XII and prekallikrein can cause isolated prolongation of APTT. Of these only deficiency of factor IX deficiency causes bleeding. Deficiency on factor XII and prekallikrein are not associated with bleeding.
    5. Isolated Prolongation of PT (Prolonged PT, Normal APTT, Prolonged TT and normal platelet count):
      1. The commonest cause of isolated prolongation of PT is a deficiency of factor VII. This may be seen in
        1. Vitamin K deficiency/Use of Warfarin type oral anticoagulants: Factors II, VII, IX and X are vitamin K dependent and have half-lives of 65hrs, 5hrs, 25hrs and 40hrs respectively. When vitamin K co-factor activity is not available either as a result of vitamin K deficiency or the use of warfarin type of oral anticoagulants, the synthesis of vitamin K dependent factors decreases.  The half-life of factor VII is considerably shorter than that of other factors and the levels of factor VII fall the earliest. This results in a prolonged PT but a normal APTT. With time other factor levels fall and the APTT also prolongs.
        2. Early Liver disease
      2. The other causes of isolated prolongation of PT include inherited factor VII deficiency, dysfibrinogenaemia or mild factor VIII, IX or IX deficiency
    6. Isolated prolongation of TT: Isolated prolongation of TT is seen in fibrinogen deficiency or dysfibrinogenaemia
    7. Coagulopathy with normal first-line coagulation tests: May be seen in platelet function defects, vascular coagulation defects, mild von Willebrand’s disease, factor XIII deficiency, disorders of fibrinolysis, dysfibrinogenaemia and α2-Plasmin inhibitor deficiency.
    8. Isolated thrombocytopenia: Isolated thrombocytopenia may be seen in bone marrow failure syndromes, immunethrombocytopenia, following viral infection and in patients with hypersplensim or inherited thrombocytopenia.

Clinical Manifestation of Iron Deficiency


The manifestations of Iron deficiency evolve insidiously and are multi-systemic. They include

Anaemia

Iron deficiency causes hypochromic microcytic anaemia. The anaemia has an insidious onset and the patient may become severely anaemic before symptoms of anaemia become evident.

Non-Specific Symptoms

Iron deficiency can cause fatigue, irritability, dizziness, breathlessness, and headache. One may attribute these symptoms to anaemia but  these symptoms are seen in patients with iron deficiency even in the absence of anaemia. Iron therapy has been shown to correct many of these manifestations.

Skin and Hair

Iron deficiency results in brittle nails that have longitudinal ridges. The nails become thin, brittle and become flat (platonychia) or concave (koilonychia). Hair may become thin and brittle.

Gastrointestinal System

Next to blood the effects of iron deficiency are most pronounced on the gastrointestinal system

  1. Tongue: Iron deficiency causes atrophy of the papillae of the tongue. The filiform papillae of the anterior part of the tongue are the first to be affected. The fungiform papillae of the posterior tongue atrophy later resulting in a smooth red tongue.  Papillary atrophy results in soreness of the tongue. The changes reverse after about 1-2 weeks of iron therapy.
  2. Mouth: Iron deficiency results in angular stomatitis. This anomalies is not specific to iron deficiency may be seen in pyridoxine and riboflavin deficiency.
  3. Dysphagia: Iron deficiency results in the formation of webs at the junction of hypopharynx and oesophagus. These manifest as dysphagia that has an insidious onset. The patients complains of discomfort on swallowing, initially for solids, at the level of the cricoid cartilage. Mild dysphagia may be corrected by iron replenishment but dysphagia persists in most patients despite iron replenishment and dilatation may be needed. Oesophageal webs predispose to carcinoma. (See Plummer-Vinson Syndrome/Peterson-Kelly Syndrome)
  4. Pica: Pica is craving for non-nutritive substances like chalk, paint and ice. Pagophagia, the craving for ice is a common form of pica.

Neuromuscular Symptoms

Iron deficiency impairs performance of muscles. Children with iron deficiency show irritability, are disruptive, have impaired attention span and may show scholastic impairment. Iron deficiency has also been shown to be associated with developmental delay, ischaemic stroke and raised intracranial pressure.

Effect on Immunity and Infections

Iron deficiency decreases the number of T lymphocytes and impairs phagocytosis. This however does not appear to result in an increased risk of infections.

Menstrual Anomalies

While menstrual anomalies can be a cause of iron deficiency, they can often be a consequence of iron deficiency. Only response to treatment can tell which of the two is the case in a given patient.

Skeletal Expansion

Young patients who have prolonged iron deficiency may develop bone changes line haemolytic anaemia or thalassaemia because of bone marrow expansion.

Clinical Types of Bleeding


The laboratory plays a central role in evaluation of a bleeding patient. Every patients with bleeding needs to be screened with a prothrombin time, activated partial thromboplastin time, thrombin time, platelet count and assessment of factor XIII. These tests help to classify the patients into one of the following groups of defects – thrombocytopenia, defects of the intrinsic coagulation system or defects of the extrinsic coagulation system. The  patterns of bleeding in disease of platelets and coagulation are sufficiently distinct to allow a clinical distinction between the two groups of bleeding disorders.

The table below gives the differences between bleeding due to a platelet/vascular disease and a coagulopathy.

Clinical Feature Platelet/Vascular Defects Coagulopathy
Gender Predilection Slight female preponderance as immunotrhrombocytopenia is more common in women Domanantly male because the commonest coagulation factor deficiencies are X linked inherited disorders
Family/Personal History of bleeding Uncommon Common
Mucosal Bleeding Common Less common
Muscle and Joint Bleeding Uncommon Typical. Dissecting haematomas seen.
Skin Bleeding Typically petechiae. Ecchymosis when present tend to few in number Typically bruising. Ecchymosis when present tend to be large and multiple
Delayed Bleeding Unusual May be present
Bleeding from superficial wounds Persistant Minimal

 

Paraneoplastic syndromes Associated with Lymphoma


Paraneoplastic synromes are non-metastatic distant manifestation of a cancer. The paraneoplastic manufestations of lymphoma aredescribed below.

Endocrine Manifestations
Hypecalcaemia: About 4% of Hodgkin’s Lymphoma and about 1% of the patinets with non-Hodgkin’s lymphoma (NHL) have hypercalcaemia. The  NHLs associated with high prevelance hypercalcaemia include high grade B-cell neoplasms and adult T cell lymphoma/leukaemia. Paraneoplastic hypercalcaemia may be caused by PTHrP or 1, 25-dihydroxy vitamin D3. Hypercalcaemia in almost all the patients of HL results from overproduction in 1,25-dihydroxy vitamin D. This mechanism is analogous of hypercalcaemia of tuberculosis and sarcoidosis, is believed to be a result of increased activity of 1α-hydroxylase in macrophages and is responsive to corticosteroids.

Among the HNLs the lymphoma with the highest incidence of hypecalcaemia is adult T-cell leukaemia/lymphoma. About one fifth to half thr patirnts have hypercalcaemia. Both PTHrP and calcetrol have been associated with hypercalcaemia.

Syndrome of Inappropriate ADH Secertion (SIADH): Paraneoplastic SIADH is most commonly associated with small cell lung cancer but has been described in patients with lymphoma. When the syndrome developes in patients with lymphoma on treatment vinca alkaloids may be the culprit.

Neurological Manifestations
Paraneoplastic Cerebellar Degeration (PCD): PCD has been reported in HL as well as NHL but the syndrome associated with HL is better characterized as HL is one of the commonest malignancies associated with PCD. HL associated PCD may occur even when the patient is in remission and there appers to be no relation of PCD and stage of HL. PCD is an immune disease that is associated with anti-Hu in cases of PCD associated with small cell lung cancer and anti-Yo antibodies in gynecological cancers. PCD associated with HL is charcterized by the presence of anti-TR antibodies that are distinct from the antibodies mentioned above. PCD associated with HL appeares to have a better outcome. Spontaneous recovery has been reported in 15% of patients and recovery following therapy has been reported. Immunosupressive therapy has not been shown to be of benefit.

Other Central Nervous System Manifestations: Limbic encephalitis that reverses with treatment, a chloroform disorders, a paraneoplastic myelopathy have been described with HL.

Motor Neuron Disease (MND): Paraneoplastic MND associated with lymphoma is charcterized by upper and lower motor neuron involvement. These patients often have paraproteinaemia. They may may benefit from chemotherapy but the benefit of immunotherapy and plasmapheresis is less clear.

Peripheral Nerve Involvement
Acute polyradiculoneuropathy (APN): APN resembles Guillian-Barre syndrome and is seen with HL. No specific antibodies have been associated with this syndrome. Treatment of HL does not appear to alter it’s course. Plasmaphersis and intravenous gamma globin may control the manifestations. Patients with relapsing and remiting forms have been described.
Polyneuropathy of Paraproteinaemia: Lymphplasmacytic lymphoma is associated with a peripheral neuropathy (sensory, motor or both) in 5-10% of the patients. The pathogenesis of these neuropathies is diverse and include

  1. Demyelination resulting from IgM monoclonal band being directed against neuronal components
  2. Axonopathies due to endoneural granulofibrilar IgM diposits lacking activity against neuronal components.
  3. Rarely amyloid deposition may cause neuropathy

Neuropathy due to Paraneoplatic Vasculitis: painful mononeuritis multiplex may occur in patinets with lymphoma. In some of these patinets the vasculitis may be limited to the nerves. Patients may respond to treatment if the primary, immunosupression or plasmapheresis.

Neuromuscular Dysfunction: Rarely patients with lymphoma may develop Eaton-Lambert stndrome or myasthenia gravis

Cutaneous Paraneoplastic Syndromes
The cutaneous paraneoplastic syndromes associated with lymphoma include acanthosis nigracans, Sweet’s syndrome (neutrophila, fever, papular rash), paraneoplastic pemphigus (most commonly asociated with CLL and NHL) and lichen planus with low grade lymphomas.

Haematological Paraneoplastic Syndromes
Sixty three pecent of the patients of lymphoma have an abnormal haemoram. Anaemia is the commonest abnormality. Warm antibody type autoimmune haemolytic anaemia has been described NHL particularly angioimmunoblastic T cell lymphoma and chronic lymphocytic leukaemia (CLL). AIHA occurs with an incidence of 2-3% in other NHLs and HL. Immune thrombocytopenia is less common than AIHA. It is most commonly seen in CLL but may be seen with other lymphomas. Low grad B cell lymphomas may be associated with cold antibody type of AIHA. Pure red cell aplasia may be seen with T cell lymphomas. Eosinophila is more common in HL and T cell lymphomas but may be seen in B cell lymphomas. Lymphoma may be a cause of secondary thrombocytosis.

Renal Paraneoplastic Syndrome
About 10% patinets with idiopathic nephrotic syndrome have an underlying maligancy. Most of these patinets have membranoproliferative glomerulonephritis. HL is associated with minimal change disease. Membranous and membranoproliferative glomerulonephritis may be seen with CLL and other NHLs. A few patients with NHLs have been reported to have minimal change disease.