Displaying items by tag: Blood Diseases and Disorders
LABORATORY TESTS IN PORPHYRIAS
Classification based on predominant clinical manifestations
|
Classification based on site of expression of disease
|
Classification based on mode of clinical presentation
|
Neuropsychiatric
|
Hepatic
|
Acute
|
1. Acute intermittent porphyria
|
1. ALA-dehydratase porphyria
|
1. ALA-dehydratase porphyria (Plumboporphyria)
|
2. ALA-dehydratase porphyria (Plumboporphyria)
|
2. Acute intermittent porphyria
|
2. Acute intermittent porphyria
|
Cutaneous (Photosensitivity)
|
3. Hereditary coproporphyria
|
3. Hereditary coproporphyria
|
1. Congenital erythropoietic porphyria
|
4. Variegate porphyria
|
4. Variegate porphyria
|
2. Porphyria cutanea tarda
|
Erythropoietic porphyria
|
Non-acute (cutaneous)
|
3. Erythropoietic protoporphyria
|
1. Congenital erythropoietic porphyria
|
1. Porphyria cutanea tarda
|
Mixed (Neuropsychiatric and cutaneous)
|
2. Erythropoietic protoporphyria
|
2. Congenital erythropoietic porphyria
|
1. Hereditary coproporphyria
|
Hepatic/Erythropoietic
|
3. Erythropoietic protoporphyria
|
2. Variegate porphyria
|
1. Porphyria cutanea tarda
|
|
Porphyria | Deficient enzyme | Clinical features | Inheritance | Initial test |
1. Acute intermittent porphyria (AIP)* | PBG deaminase | Acute neurovisceral attacks; triggering factors+ (e.g. drugs, diet restriction) | Autosomal dominant | Urinary PBG; urine becomes brown, red, or black on standing |
2. Variegate porphyria | Protoporphyrinogen oxidase | Acute neurovisceral attacks + skin fragility, bullae | Autosomal dominant | Urinary PBG |
3. Hereditary coproporphyria | Coproporphyrinogen oxidase | Acute neurovisceral attacks + skin fragility, bullae | Autosomal dominant | Urinary PBG |
4. Congenital erythropoietic porphyria | Uroporphyrinogen cosynthase | Onset in infancy; skin fragility, bullae; extreme photosensitivity with mutilation; red teeth and urine (pink red urinestaining of diapers) | Autosomal recessive | Urinary/fecal total porphyrins; ultraviolet fluorescence of urine, feces, and bones |
5. Porphyria cutanea tarda* | Uroporphyrinogen decarboxylase | Skin fragility, bullae | Autosomal dominant (some cases) | Urinary/fecal total porphyrins |
6. Erythropoietic protoporphyria* | Ferrochelatase | Acute photosensitivity | Autosomal dominant | Free erythrocyte protoporphyrin |
Disorders marked with * are the three most common porphyrias. PBG: Porphobilinogen |



- 10-20 ml of fresh random urine sample without any preservative;
- 5-10 g wet weight of fecal sample, and
- blood anticoagulated with EDTA.
Porphyria | Urine | Feces |
Acute intermittent porphyria | PBG, Copro III | – |
Variegate porphyria | PBG, Copro III | Proto IX |
Hereditary coproporphyria | PBG, Copro III | Copro III |
PBG: Porphobilinogen; Copro III: Coproporphyrinogen III; Proto IX: Protoporphyrin IX |
Porphyria | Urine | Feces | Erythrocytes |
Congenital erythropoietic porphyria | Uro I, Copro I | Copro I | – |
Porphyria cutanea tarda | Uroporphyrin | Isocopro | – |
Erythropoietic protoporphyria | – | – | Protoporphyrin |
Uro I: Uroporphyrinogen I; Copro I: Coproporphyrinogen I; Isocopro: Isocoproporphyrinogen |
PLATELET GLYCOPROTEIN ANALYSIS
Fresh platelets should always be used. Storing platelets dramatically changes the level of transmembrane proteins. The best way is to follow one of standardized protocols defined in: Immunophenotypic analysis of platelets. Krueger LA, Barnard MR, Frelinger AL 3rd, Furman MI, Michelson AD.Curr Protoc Cytom. 2002 Feb;Chapter 6:Unit 6.10.
TEST FOR D-DIMER
TEST FOR FIBRINOGEN/FIBRIN DEGRADATION PRODUCTS (FDPs)
Platelet Aggregation Studies
Platelet aggregation tests are carried out in specialized hematology laboratories if platelet dysfunction is suspected. These tests are usually indicated in patients presenting with mucocutaneous type of bleeding and in whom screening tests reveal normal platelet count, prolonged bleeding time, normal prothrombin time, and normal activated partial thromboplastin time.
MORPHOLOGY OF PLATELETS

NUMERICAL ABNORMALITIES OF LEUKOCYTES
- Acute bacterial infections: Abscess, pneumonia, meningitis, septicemia, acute rheumatic fever, urinary tract infection.
- Tissue necrosis: Burns, injury, myocardial infarction.
- Acute blood loss
- Acute hemorrhage
- Myeloproliferative disorders
- Metabolic disorders: Uremia, acidosis, gout
- Poisoning
- Malignant tumors
- Physiologic causes: Exercise, labor, pregnancy, emotional stress.
- Severe bacterial infections, e.g. septicemia, pneumonia
- Severe hemorrhage
- Severe acute hemolysis
- Poisoning
- Burns
- Carcinoma metastatic to bone marrow Leukemoid reaction should be differentiated from chronic myeloid leukemia (Table 801.1).


- Infections
(a) Bacterial: typhoid, paratyphoid, miliary tuberculosis, septicemia
(b) Viral: influenza, measles, rubella, infectious mononucleosis, infective hepatitis.
(c) Protozoal: malaria, kala azar
(d) Overwhelming infection by any organism - Hematologic disorders: megaloblastic anemia, aplastic anemia, aleukemic leukemia, myelophthisis.
- Drugs:
(a) Idiosyncratic action: Analgesics, antibiotics, sulfonamides, phenothiazines, antithyroid drugs, anticonvulsants.
(b) Dose-related: Anticancer drugs - Ionizing radiation
- Congenital disorders: Kostman's syndrome, cyclic neutropenia, reticular dysgenesis.
- Neonatal isoimmune neutropaenia
- Systemic lupus erythematosus
- Felty's syndrome
- Hypersplenism
- Allergic diseases: Bronchial asthma, rhinitis, urticaria, drugs.
- Skin diseases: Eczema, pemphigus, dermatitis herpetiformis.
- Parasitic infection with tissue invasion: Filariasis, trichinosis, echinococcosis.
- Hematologic disorders: Chronic Myeloproliferative disorders, Hodgkin's disease, peripheral T cell lymphoma.
- Carcinoma with necrosis.
- Radiation therapy.
- Lung diseases: Loeffler's syndrome, tropical eosinophilia
- Hypereosinophilic syndrome.
- Infections: Tuberculosis, subacute bacterial endocarditis, malaria, kala azar.
- Recovery from neutropenia.
- Autoimmune disorders.
- Hematologic diseases: Myeloproliferative disorders, monocytic leukemia, Hodgkin's disease.
- Others: Chronic ulcerative colitis, Crohn's disease, sarcoidosis.

- Infections:
(a) Viral: Acute infectious lymphocytosis, infective hepatitis, cytomegalovirus, mumps, rubella, varicella
(b) Bacterial: Pertussis, tuberculosis
(c) Protozoal: Toxoplasmosis - Hematological disorders: Acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, lymphoma.
- Other: Serum sickness, post-vaccination, drug reactions.
WHITE BLOOD CELLS MORPHOLOGY
- Polymorphonuclear neutrophil: Neutrophil measures 14-15 μm in size. Its cytoplasm is colorless or lightly eosinophilic and contains multiple, small, fine, mauve granules. Nucleus has 2-5 lobes that are connected by fine chromatin strands. Nuclear chromatin is condensed and stains deep purple in color. A segmented neutrophil has at least 2 lobes connected by a chromatin strand. A band neutrophil shows non-segmented U-shaped nucleus of even width. Normally band neutrophils comprise less than 3% of all leukocytes. Majority of neutrophils have 3 lobes, while less than 5% have 5 lobes. In females, 2-3% of neutrophils show a small projection (called drumstick) on the nuclear lobe. It represents one inactivated X chromosome.
- Eosinophil: Eosinophils are slightly larger than neutrophils (15-16 μm). The nucleus is often bilobed and the cytoplasm is packed with numerous, large, bright orange-red granules. On blood smears, some of the eosinophils are often ruptured.
- Basophils: Basophils are seen rarely on normal smears. They are small (9-12 μm), round to oval cells, which contain very large, coarse, deep purple granules. It is difficult to make out the nucleus since granules cover it.
- Monocytes: Monocyte is the largest of the leukocytes (15-20 μm). It is irregular in shape, with oval or clefted (kidney-shaped) nucleus and fine, delicate chromatin. Cytoplasm is abundant, bluegray with ground glass appearance and often contains fine azurophil granules and vacuoles. After migration to the tissues from blood, they are called as macrophages.
- Lymphocytes: On peripheral blood smear, two types of lymphocytes are distinguished: small and large. The majority of lymphocytes are small (7-8 μm). These cells have a high nuclearcytoplasmic ratio with a thin rim of deep blue cytoplasm. The nucleus is round or slightly clefted with coarsely clumped chromatin. Large lymphocytes (10-15 μm) have a more abundant, pale blue cytoplasm, which may contain a few azurophil granules. Nucleus is oval or round and often placed on one side of the cell.

Toxic granules: These are darkly staining, bluepurple, coarse granules in the cytoplasm of neutrophils. They are commonly seen in severe bacterial infections.
- Döhle inclusion bodies: These are small, oval, pale blue cytoplasmic inclusions in the periphery of neutrophils. They represent remnants of ribosomes and rough endoplasmic reticulum. They are often associated with toxic granules and are seen in bacterial infections.
- Cytoplasmic vacuoles: Vacuoles in neutrophils are indicative of phagocytosis and are seen in bacterial infections.
- Shift to left of neutrophils: This refers to presence of immature cells of neutrophil series (band forms and metamyelocytes) in peripheral blood and occurs in infections and inflammatory disorders.
- Hypersegmented neutrophils: Hypersegmentation of neutrophils is said to be present when >5% of neutrophils have 5 or more lobes. They are large in size and are also called as macropolycytes. They are seen in folate or vitamin B12 deficiency and represent one of the earliest signs.
- Pelger-Huet cells: In Pelger-Huet anomaly (a benign autosomal dominant condition), there is failure of nuclear segmentation of granulocytes so that nuclei are rod-like, round, or have two segments. Such granulocytes are also observed in myeloproliferative disorders (pseudo-Pelger-Huet cells).
- Atypical lymphocytes: These are seen in viral infections, especially infectious mononucleosis. Atypical lymphocytes are large, irregularly shaped lymphocytes with abundant cytoplasm and irregular nuclei. Cytoplasm shows deep basophilia at the edges and scalloping of borders. Nuclear chromatin is less dense and occasional nucleolus may be present.
- Blast cells: These are most premature of the leukocytes. They are large (15-25 μm), round to oval cells, with high nuclear cytoplasmic ratio. Nucleus shows one or more nucleoli and nuclear chromatin is immature. These cells are seen in severe infections, infiltrative disorders, and leukemia. In leukemia and lymphoma, blood smear suggests the diagnosis or differential diagnosis and helps in ordering further tests (see Figure 800.2 and Box 800.1).

RED CELLS MORPHOLOGY

- Red cells with abnormal size (see Figure 799.1)
- Red cells with abnormal staining
- Red cells with abnormal shape (see Figure 799.1)
- Red cell inclusions (see Figure 799.2)
- Immature red cells (see Figure799.3)
- Abnormal red cell arrangement(see Figure 799.4).
Macrocytes are red cells larger in size than normal. Oval macrocytes (macro-ovalocytes) are seen in megaloblastic anemia, myelodysplastic syndrome, and in patients being treated with cancer chemotherapy. Round macrocytes are seen in liver disease, alcoholism, and hypothyroidism.
Staining intensity of red cells depends on hemoglobin content. Red cells with increased area of central pallor (i.e. containing less hemoglobin) are called as hypochromic. They are seen when hemoglobin synthesis is defective, i.e. in iron deficiency, thalassemias, anaemia of chronic disease, and sideroblastic anemia.
Basophilic stippling or punctate basophilia refers to the presence of numerous, irregular basophilic (purple-blue) granules which are uniformly distributed in the red cell. These granules represent aggregates of ribosomes. Their presence is indicative of impaired erythropoiesis and they are seen in thalassemias, megaloblastic anemia, heavy metal poisoning (e.g. lead), and liver disease.cell. These granules represent aggregates of ribosomes. Their presence is indicative of impaired erythropoiesis and they are seen in thalassemias, megaloblastic anemia, heavy metal poisoning (e.g. lead), and liver disease.

Pappenheimer bodies are basophilic, small, ironcontaining granules in red cells. They give positive Perl's Prussian blue reaction. Unlike basophilic stippling, Pappenheimer bodies are few in number and are not distributed throughout the red cell. They are seen following splenectomy and in thalassemias and sideroblastic anemia.
Cabot's rings are fine, reddish-purple or red, ring-like structures. They appear like loops or figure of eight structures. They indicate impaired erythropoiesis and are seen in megaloblastic anemia and lead poisoning.


Autoagglutination refers to the clumping of red cells in large, irregular groups on blood smear. It is seen in cold agglutinin disease. Role of blood smear in anemia is shown in Box 799.1 and Figures 799.5 to 799.7.


