- Published on
Pathology - Aplastic Anemia
Aplastic anemia may occur after carbamazepine medication and subsequently developed invasive aspergillosis. Aplastic anemia originates from defective or inadequate multipotent myeloid stem cells (acquired or hereditary), or antigen receptor change causing T-cell activated stem cell suppression (caused by medications, infection, or other factors). The result is decreased erythrocytes, leukocytes, and platelets, known as pancytopenia.
Bone marrow is hypocellular with fatty infiltration. Aplastic anemia is more typically idiopathic, and myelotoxic medicines (alkylating agents, antimetabolites) most commonly employed for cancer therapy generate doserelated suppression. However, certain drugs might result in aplastic anemia in an unanticipated form, including carbamazepine (first-line treatment of TN), chloram-phenicol, streptomycin, hydralazine, and indomethacin to mention a few. Medication side effects might be overwhelming, but it is most important to concentrate on the most prevalent and the most serious. Aplastic anemia can result in significant infection (by opportunistic organisms as in this case) from neutropenia and bleeding from thrombocytopenia. Other causes include certain viruses (parvovirus B19, EBV, HIV) and Fanconi’s anemia.
Aplastic anemia may occur after carbamazepine medication and subsequently developed invasive aspergillosis. Aplastic anemia originates from defective or inadequate multipotent myeloid stem cells (acquired or hereditary), or antigen receptor change causing T-cell activated stem cell suppression (caused by medications, infection, or other factors). The result is decreased erythrocytes, leukocytes, and platelets, known as pancytopenia.
Bone marrow is hypocellular with fatty infiltration. Aplastic anemia is more typically idiopathic, and myelotoxic medicines (alkylating agents, antimetabolites) most commonly employed for cancer therapy generate doserelated suppression. However, certain drugs might result in aplastic anemia in an unanticipated form, including carbamazepine (first-line treatment of TN), chloram-phenicol, streptomycin, hydralazine, and indomethacin to mention a few. Medication side effects might be overwhelming, but it is most important to concentrate on the most prevalent and the most serious. Aplastic anemia can result in significant infection (by opportunistic organisms as in this case) from neutropenia and bleeding from thrombocytopenia. Other causes include certain viruses (parvovirus B19, EBV, HIV) and Fanconi’s anemia.
- Published on
Pathology - Sickle-Cell Anemia
Sickle-cell anemia is an autosomal recessive disorder most commonly encountered in African Americans. Sickle hemoglobin (HbS) is the result of a missense mutation of valine for glutamic acid at the sixth position of the β-globulin chain. Patients homozygous for the sickle-cell gene (HbSS) do not produce any normal HbA and develop anemia starting around 6 to 9 months of life, resulting from decreased HbF and increased production of HbS. Deoxy-genated hemoglobin molecules cluster and polymerize into needle-like fibers, causing the erythrocytes to assume a sickle shape. Recurrent sickling produces membrane damage and intravascular hemolysis. In addition, aberrant cell shape results in microvascular occlusion, which can trigger pain crises, such as in bones, the lungs, or penis (priapism). Dactylitis (painful swelling of the hands and feet) in infants due to bone infarcts is a common initial presenting symptom; however, the most frequent presentation is painless hematuria.
Autosplenectomy (associated with Howell-Jolly bodies present on peripheral smear) often occurs by 2 years of age, which increases risk for infection by encapsulated organisms (e.g., pneumococcus, Neisseria, Salmonella). Family history is frequently notable, like with this child’s uncle who presumably died of sickle-cell problems. The heterozygous condition (HbS, sickle-cell trait) does not result in anemia and conveys resistance to Plasmodium falciparum malaria.
Sickle-cell anemia is an autosomal recessive disorder most commonly encountered in African Americans. Sickle hemoglobin (HbS) is the result of a missense mutation of valine for glutamic acid at the sixth position of the β-globulin chain. Patients homozygous for the sickle-cell gene (HbSS) do not produce any normal HbA and develop anemia starting around 6 to 9 months of life, resulting from decreased HbF and increased production of HbS. Deoxy-genated hemoglobin molecules cluster and polymerize into needle-like fibers, causing the erythrocytes to assume a sickle shape. Recurrent sickling produces membrane damage and intravascular hemolysis. In addition, aberrant cell shape results in microvascular occlusion, which can trigger pain crises, such as in bones, the lungs, or penis (priapism). Dactylitis (painful swelling of the hands and feet) in infants due to bone infarcts is a common initial presenting symptom; however, the most frequent presentation is painless hematuria.
Autosplenectomy (associated with Howell-Jolly bodies present on peripheral smear) often occurs by 2 years of age, which increases risk for infection by encapsulated organisms (e.g., pneumococcus, Neisseria, Salmonella). Family history is frequently notable, like with this child’s uncle who presumably died of sickle-cell problems. The heterozygous condition (HbS, sickle-cell trait) does not result in anemia and conveys resistance to Plasmodium falciparum malaria.
- Published on
Pathology - α-thalassemia trait
α-thalassemia trait (minor), a disease of α-chain synthesis more typically reported in African American and southeastern Asian cultures. In this variation, two α-chain deletions exist. In African Americans, the losses are on separate chromosomes (α/- α/-), but the losses are on the same chromosome (-/- α/α) in Asians. The lack of two chains results in a global drop in all normal adult hemoglobin synthesis (HbA, HbA 2 , HbF); consequently, the electrophoresis is normal (relative quantities are the same as all hemoglobin types require the α-chain and are equally affected). With normal ferritin, the diagnosis is made by microcytic anemia and an elevated erythrocyte count, which is peculiar to thalassemias in anemias. Teardrop erythrocytes are a result of membrane damage due to removal of excess globin. Other α-thalassemias result from deletion of one, three, and four α-chains. One deletion produces an asymptomatic carrier without anemia. Three deletions generate hemoglobin H (HbH) illness, which produces a severe hemolytic anemia with HbH (four β-chains) identifiable by electrophoresis. Four deletions resulted in hemoglobin Bart (four γ-chains) illness, which creates hydrops fetalis in utero and is incompatible with life.
α-thalassemia trait (minor), a disease of α-chain synthesis more typically reported in African American and southeastern Asian cultures. In this variation, two α-chain deletions exist. In African Americans, the losses are on separate chromosomes (α/- α/-), but the losses are on the same chromosome (-/- α/α) in Asians. The lack of two chains results in a global drop in all normal adult hemoglobin synthesis (HbA, HbA 2 , HbF); consequently, the electrophoresis is normal (relative quantities are the same as all hemoglobin types require the α-chain and are equally affected). With normal ferritin, the diagnosis is made by microcytic anemia and an elevated erythrocyte count, which is peculiar to thalassemias in anemias. Teardrop erythrocytes are a result of membrane damage due to removal of excess globin. Other α-thalassemias result from deletion of one, three, and four α-chains. One deletion produces an asymptomatic carrier without anemia. Three deletions generate hemoglobin H (HbH) illness, which produces a severe hemolytic anemia with HbH (four β-chains) identifiable by electrophoresis. Four deletions resulted in hemoglobin Bart (four γ-chains) illness, which creates hydrops fetalis in utero and is incompatible with life.
- Published on
Pathology - Iron Deficiency Anemia
Iron-deficiency anemia is most likely linked to GI hemorrhage. Iron-deficiency anemia is the most common anemia, typically due to loss of iron from chronic bleeding; however, decreased intake, increased utilization (pregnant women, infants), malabsorptive disorders (celiac’s disease), and some hemoglobinopathies (paroxysmal nocturnal hemoglobinuria) can also be causative. As iron reserves drop, so does serum ferritin (which is the protein bound physiologically accessible form of iron). The TIBC of transferrin increases to maximize use of available iron; nevertheless, the fraction of saturated binding sites decreases due to shortage of available iron. In summary, test data demonstrate decreased serum iron, ferritin, and hemoglobin saturation with increased TIBC. Any unexplained iron-deficiency anemia in an older patient (postmenopausal woman) with a positive FOBT should trigger a colonoscopy to rule-out colon cancer. TSH is tested to rule-out hypothyroidism and liver function tests to screen for harmful side effects of simvastatin as causes of the patient’s presenting problems.
Iron-deficiency anemia is most likely linked to GI hemorrhage. Iron-deficiency anemia is the most common anemia, typically due to loss of iron from chronic bleeding; however, decreased intake, increased utilization (pregnant women, infants), malabsorptive disorders (celiac’s disease), and some hemoglobinopathies (paroxysmal nocturnal hemoglobinuria) can also be causative. As iron reserves drop, so does serum ferritin (which is the protein bound physiologically accessible form of iron). The TIBC of transferrin increases to maximize use of available iron; nevertheless, the fraction of saturated binding sites decreases due to shortage of available iron. In summary, test data demonstrate decreased serum iron, ferritin, and hemoglobin saturation with increased TIBC. Any unexplained iron-deficiency anemia in an older patient (postmenopausal woman) with a positive FOBT should trigger a colonoscopy to rule-out colon cancer. TSH is tested to rule-out hypothyroidism and liver function tests to screen for harmful side effects of simvastatin as causes of the patient’s presenting problems.
- Published on
Pathology - β-thalassemia major
β-thalassemia major is established by the lack of HbA 1 (composed of α-2 and β-2) on electrophoresis.
In contrast to heterozygous β-thalassemia minor, the patient is homozygous for deletion of the β-hemoglobin gene.
Therefore, absence of β-chain synthesis enhances production of HbA 2 (α-2, δ-2) and HbF (α-2, γ-2). The anemia is a result of inefficient erythropoiesis; nevertheless, breakdown products of excess α-chains also results in intramedullary destruction of RBC precursors and peripheral hemolysis. The overall loss in hemoglobin results in a microcytic, hypochromic anemia. Resulting tissue hypoxia drives EPO production, which causes marrow growth and bone deformity, as evidenced by the hypertrophied mandible of this infant. Increased iron absorption from marrow expansion coupled with transfusion-dependent survival often results in heart failure owing to hemochromatosis.
Patients with β-thalassemia minor are largely asymptomatic unless rarely during pregnancy.
β-thalassemia major is established by the lack of HbA 1 (composed of α-2 and β-2) on electrophoresis.
In contrast to heterozygous β-thalassemia minor, the patient is homozygous for deletion of the β-hemoglobin gene.
Therefore, absence of β-chain synthesis enhances production of HbA 2 (α-2, δ-2) and HbF (α-2, γ-2). The anemia is a result of inefficient erythropoiesis; nevertheless, breakdown products of excess α-chains also results in intramedullary destruction of RBC precursors and peripheral hemolysis. The overall loss in hemoglobin results in a microcytic, hypochromic anemia. Resulting tissue hypoxia drives EPO production, which causes marrow growth and bone deformity, as evidenced by the hypertrophied mandible of this infant. Increased iron absorption from marrow expansion coupled with transfusion-dependent survival often results in heart failure owing to hemochromatosis.
Patients with β-thalassemia minor are largely asymptomatic unless rarely during pregnancy.
- Published on
Pathology - Tetanus
A highly infected wound may requires tetanus treatment. A highly contaminated wound with no history of tetanus vaccine requires tetanus and diphtheria (Td) toxoid as well as tetanus immune globulin (TIG).
Previously immunized patients do not require TIG and only require the Td toxoid if it has been greater than 5 years since their last immunization. Clean, mild wounds require Td toxoid only for unvaccinated patients (or patients with incomplete vaccination series) or those who have greater than 10 years since their last vaccine. TIG is not typically given for clean, small wounds.
A highly infected wound may requires tetanus treatment. A highly contaminated wound with no history of tetanus vaccine requires tetanus and diphtheria (Td) toxoid as well as tetanus immune globulin (TIG).
Previously immunized patients do not require TIG and only require the Td toxoid if it has been greater than 5 years since their last immunization. Clean, mild wounds require Td toxoid only for unvaccinated patients (or patients with incomplete vaccination series) or those who have greater than 10 years since their last vaccine. TIG is not typically given for clean, small wounds.
- Published on
Pathology - Hyperacute Rejection of Transplant
This irreversible type II hypersensitivity reaction of preformed recipient alloantibodies to either the ABO blood group or HLA class I antigens on the graft endothelium occurs within minutes to maybe hours. The binding of the antibodies promotes release of particles that promote coagulation and cytokines that recruit inflammatory mediators. The graft tissue is destroyed through vascular thrombosis and rapid organ death as described in this patient. It is now rare due to good ABO screening and HLA crossmatching.
Patients who are most prone to have this occur are often listed with the highest priority for a graft. Preformed antibodies may result from many transfusions, several pregnancies, or prior transplants.
This irreversible type II hypersensitivity reaction of preformed recipient alloantibodies to either the ABO blood group or HLA class I antigens on the graft endothelium occurs within minutes to maybe hours. The binding of the antibodies promotes release of particles that promote coagulation and cytokines that recruit inflammatory mediators. The graft tissue is destroyed through vascular thrombosis and rapid organ death as described in this patient. It is now rare due to good ABO screening and HLA crossmatching.
Patients who are most prone to have this occur are often listed with the highest priority for a graft. Preformed antibodies may result from many transfusions, several pregnancies, or prior transplants.
- Published on
Pathology - Graft Versus Host Disease
This reaction is a potential complication in bone marrow and liver transplants and is the result of T lymphocytes from donor transplant product perceiving the host tissues as foreign. The responding donor T cells activate CD4 + and CD8 + T cells in the host, inducing lymphocytic infiltration of the skin, GI tract, and liver. Damage to these organs creates the distinctive clinical signs including dermatitis, crampy stomach pain with bloody diarrhea and/or anorexia, cholestasis producing jaundice and probably hepatocellular necrosis, as well as fever. Severity of symptoms predicts mortality. The reaction may occur in days to weeks following transplant. Posttransplant immunosuppression and ways to eliminate T cells from donor tissue has lowered the incidence, although it is still relatively common. The conventional treatment consists of injectable glucocorticoids, which require careful tapering.
This reaction is a potential complication in bone marrow and liver transplants and is the result of T lymphocytes from donor transplant product perceiving the host tissues as foreign. The responding donor T cells activate CD4 + and CD8 + T cells in the host, inducing lymphocytic infiltration of the skin, GI tract, and liver. Damage to these organs creates the distinctive clinical signs including dermatitis, crampy stomach pain with bloody diarrhea and/or anorexia, cholestasis producing jaundice and probably hepatocellular necrosis, as well as fever. Severity of symptoms predicts mortality. The reaction may occur in days to weeks following transplant. Posttransplant immunosuppression and ways to eliminate T cells from donor tissue has lowered the incidence, although it is still relatively common. The conventional treatment consists of injectable glucocorticoids, which require careful tapering.
- Published on
Pathology - Pneumococcal Conjugate Vaccine in Sickle-Cell Disease
This patient may has functional asplenia secondary to splenic infarct from sickle-cell anemia. The objective of vignettes like this is to recognize what preventative measures are appropriate for certain patient groups. Patients with functional or surgical asplenia are at higher sensitivity to encapsulated pathogens such as pneumococcus. Although this patient should have had the pneumococcal conjugated vaccination, it is suggested that patients with asplenia additionally obtain the pneumococcal polysaccharide vaccine due to its extended number of serotypes covered. It is important to highlight that this patient is also sensitive to organisms such as Neisseria and Haemophilus . This patient should additionally receive the meningococcal and Haemophilus influenzae B vaccines if he has not already.
This patient may has functional asplenia secondary to splenic infarct from sickle-cell anemia. The objective of vignettes like this is to recognize what preventative measures are appropriate for certain patient groups. Patients with functional or surgical asplenia are at higher sensitivity to encapsulated pathogens such as pneumococcus. Although this patient should have had the pneumococcal conjugated vaccination, it is suggested that patients with asplenia additionally obtain the pneumococcal polysaccharide vaccine due to its extended number of serotypes covered. It is important to highlight that this patient is also sensitive to organisms such as Neisseria and Haemophilus . This patient should additionally receive the meningococcal and Haemophilus influenzae B vaccines if he has not already.
- Published on
Pathology - Wiskott - Aldrich Syndrome
Symptomatic triad of Wiskott–Aldrich syndrome (WAS) involves T hrombocytopenia, recurrent sinopulmonary I nfections, and E czema (mnemonic: TIE). WAS is an X-linked recessive disorder characterized by poor cell-mediated immunity and decreased IgM production through gradual deletion of T and B cells. The pathogenesis comes from a null-mutation in the gene that codes the WAS protein (WASP), a regulator of actin polymerization in hematopoietic cells. This leads in the absence of a particular glycoprotein receptor on T cells and platelets, resulting to a poor response to polysaccharide vaccines and to thrombocytopenia, respectively.
Megakaryocyte levels are typical. Splenomegaly can arise attributable to splenic sequestration of platelets, due to the faulty receptor and so contributing to the thrombocytopenia. Petechiae are small hemorrhages within the skin that are a sign of reduced platelets. Levels of IgG will be normal and IgA and IgE may be normal or elevated. Patients are prone to bacterial, viral, and fungal infections and also have a high frequency of autoimmune diseases and lymphoreticular cancers. Bone marrow transplantation may be useful as treatment.
Symptomatic triad of Wiskott–Aldrich syndrome (WAS) involves T hrombocytopenia, recurrent sinopulmonary I nfections, and E czema (mnemonic: TIE). WAS is an X-linked recessive disorder characterized by poor cell-mediated immunity and decreased IgM production through gradual deletion of T and B cells. The pathogenesis comes from a null-mutation in the gene that codes the WAS protein (WASP), a regulator of actin polymerization in hematopoietic cells. This leads in the absence of a particular glycoprotein receptor on T cells and platelets, resulting to a poor response to polysaccharide vaccines and to thrombocytopenia, respectively.
Megakaryocyte levels are typical. Splenomegaly can arise attributable to splenic sequestration of platelets, due to the faulty receptor and so contributing to the thrombocytopenia. Petechiae are small hemorrhages within the skin that are a sign of reduced platelets. Levels of IgG will be normal and IgA and IgE may be normal or elevated. Patients are prone to bacterial, viral, and fungal infections and also have a high frequency of autoimmune diseases and lymphoreticular cancers. Bone marrow transplantation may be useful as treatment.
