Folic acid Deficiency Anemia

A common, slowly progressive megaloblastic anemia, folic acid deficiency anemia is most prevalent in infants, adolescents, pregnant and lactating females, alcoholics, elderly people, and people with malignant or intestinal diseases.

Causes
Folic acid deficiency anemia results from a decreased level or lack of folate, a vitamin that’s essential for red blood cell production and maturation. 

Causes include:

• alcohol abuse (may suppress metabolic effects of folate)
• inadequate diet (common in alcoholics, elderly people who live alone, and infants, especially those with infections or diarrhea)
• impaired absorption (due to intestinal dysfunction from such disorders as celiac disease, tropical sprue, and regional jejunitis and from bowel resection)
• bacteria competing for available folic acid
• overcooking, which can destroy a high percentage of folic acids in foods
• limited storage capacity in infants
• prolonged drug therapy (with anticonvulsants and estrogens)
• increased folic acid requirement during pregnancy, during rapid growth in infancy (common because of increased survival rate of preterm infants), during childhood and adolescence (because of general use of folate-poor cow’s milk), and in patients with neoplastic diseases and some skin diseases (chronic exfoliative dermatitis).

Treatment Options for Thalassemia Major

Before chronic transfusions are initiated, the diagnosis of Beta-thalassemia should be confirmed and the parents counseled about this lifelong therapy. Initiating transfusion and chelation therapy can be difficult for parents to face early in their child’s life.

If there is the possibility of a bone marrow transplant, the blood should be negative for cytomegalovirus and irradiated.

Blood Transfusion therapy:
Transfusion therapy promotes general health and well-being and avoids the consequences of ineffective erythropoiesis. A transfusion program generally requires monthly transfusions, with the pretransfusion hemoglobin level >9.5 and <10.5 g/dL. In patients with cardiac disease, higher pretransfusion hemoglobin levels may be beneficial. Some blood centers have donor programs that pair donors and recipients, decreasing the exposure to multiple red cell antigens.

Transfusional hemosiderosis causes many of the complications of thalassemia major. Accurate assessment of excessive iron stores is essential to optimal therapy. The serum ferritin level is useful in assessing iron balance trends, but does not accurately predict quantitative iron stores. Undertreatment or overtreatment of presumed excessive iron stores can occur when a patient is managed based on the serum ferritin level alone.

Summary of Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP), thrombocytopenia that results from immunologic platelet destruction, may be acute (postviral thrombocytopenia) or chronic (Werlhof’s disease, purpura hemorrhagica, essential thrombocytopenia, autoimmune thrombocytopenia). Acute ITP usually affects children between ages 2 and 6; chronic ITP mainly affects adults younger than age 50, especially women between ages 20 and 40.

Causes
ITP may be an autoimmune disorder because antibodies that reduce the life span of platelets have been found in nearly all patients. The spleen probably helps to remove platelets modified by the antibody. Acute ITP usually follows a viral infection, such as rubella and chickenpox, and can follow immunization with a live virus vaccine. Chronic ITP seldom follows infection and is commonly linked to immunologic disorders, such as systemic lupus erythematosus or human immunodeficiency virus infection. It’s also linked to drug reactions.

Clinical Features
Signs and symptoms of ITP common to all forms of thrombocytopenia include petechiae, ecchymoses, and mucosal bleeding from the mouth, nose, and GI tract. Generally, hemorrhage is a rare physical finding. Purpuric lesions may occur in vital organs, such as the lungs, kidneys, or brain, and may prove fatal.
With acute ITP, which is common in children, onset is usually sudden and without warning, causing easy bruising, epistaxis, and bleeding gums. Onset of chronic ITP is insidious.

Understanding Bone marrow Transplantation

In bone marrow transplantation, usually 500 to 700 ml of marrow is aspirated from the pelvic bones of a human leukocyte antigen (HLA)–compatible donor (allogeneic) or of the recipient himself during periods of complete remission (autologous). The aspirated marrow is filtered and then infused into the recipient in an attempt to repopulate the patient’s marrow with normal cells.
This procedure has effected long-term, healthy survivals in about half of the patients with severe aplastic anemia. Bone marrow transplantation may also be effective in treating patients with acute leukemia, certain immunodeficiency diseases, and solid-tumor cancers.
Because bone marrow transplantation carries serious risks, it requires strict adherence to infection protection techniques and strict aseptic technique. It also requires that a primary caregiver provide consistent care and continuous monitoring of the patient’s status.

Before bone marrow infusion

• Explain to the patient that the success rate depends on the stage of the disease and on finding an HLA-identical sibling match.
• After bone marrow aspiration is completed under local anesthetic, apply pressure dressings to the donor’s aspiration sites. Observe the sites for bleeding. Relieve pain with an analgesic and ice packs as needed.
• Assess the patient’s understanding of bone marrow transplantation. If necessary, correct any misconceptions about the procedure and provide additional information. Prepare the patient to expect an extended facility stay. Explain that chemotherapy and, possibly, radiation therapy are necessary to remove cells that may cause the body to reject the transplant.
• Various treatment protocols are used. For example, I.V. cyclophosphamide may be used with additional chemotherapeutic agents or total body irradiation to suppress the patient’s immune system and requires aggressive hydration to prevent hemorrhagic cystitis. Control nausea and vomiting with an antiemetic (such as ondansetron, prochlorperazine, or metoclopramide) as needed. Give allopurinol, as prescribed, to prevent hyperuricemia resulting from tumor breakdown products. Because alopecia is a common adverse effect of high-dose cyclophosphamide therapy, encourage the patient to choose a wig or scarf before treatment begins.
• Total body irradiation (in one dose or several daily doses) follows chemotherapy, inducing total marrow aplasia. Warn the patient that cataracts, GI disturbances, and sterility are possible adverse effects.

Sideroblastic Anemias

Sideroblastic anemias, a group of heterogenous disorders, produce a common defect—failure to use iron in hemoglobin (Hb) synthesis, despite the availability of adequate iron stores. These anemias may be hereditary or acquired; the acquired form, in turn, can be primary or secondary.
Hereditary sideroblastic anemia often responds to treatment with pyridoxine. Correction of the secondary acquired form depends on the causative disorder; the primary acquired (idiopathic) form, however, resists treatment and usually proves fatal within 10 years after onset of complications or a concomitant disease.

Pathophysiology
Hereditary sideroblastic anemia appears to be transmitted by X-linked inheritance, occurring mostly in young males; females are carriers and usually show no signs of this disorder.
The acquired form may be secondary to ingestion of, or exposure to, toxins, such as alcohol and lead, or to drugs, such as isoniazid and chloramphenicol. It can also occur as a complication of other diseases, such as rheumatoid arthritis, lupus erythematosus, multiple myeloma, tuberculosis, and severe infections.
The primary acquired form, known as refractory anemia with ringed sideroblasts, is most common in elderly people. It’s often associated with thrombocytopenia or leukopenia as part of a myelodysplastic syndrome.
In sideroblastic anemia, normoblasts fail to use iron to synthesize Hb. As a result, iron is deposited in the mitochondria of normoblasts, which are then called ringed sideroblasts.

Chronic Lymphocytic Leukemia

A generalized, progressive disease that’s common in elderly people, chronic lymphocytic leukemia is marked by an uncontrollable spread of abnormal, small lymphocytes in lymphoid tissue, blood, and bone marrow. The prognosis is poor if anemia, thrombocytopenia, neutropenia, bulky lymphadeno-pathy, or severe lymphocytosis is present.
Nearly all patients with chronic lymphocytic leukemia are men older than age 50. According to the American Cancer Society, chronic lymphocytic leukemia accounts for almost one-third of new leukemia cases annually.

Causes
Although the cause of chronic lymphocytic leukemia is unknown, researchers suspect hereditary factors (higher incidence has been recorded within families), still-undefined chromosome abnormalities, and certain immunologic defects (such as ataxia-telangiectasia or acquired agammaglobulinemia). The disease doesn’t seem to be associated with radiation exposure.

Signs and symptoms
Chronic lymphocytic leukemia is the most benign and the most slowly progressive form of leukemia. Signs and symptoms derive from the infiltration of leukemic cells in bone marrow, lymphoid tissue, and organ systems.

Early stages
In early stages, patients usually complain of fatigue, malaise, fever, and nodal enlargement. They’re particularly susceptible to infection, which may be fatal.

Disseminated Intravascular Coagulation

Introduction

Also called consumption coagulopathy and defibrination syndrome, disseminated intravascular coagulation (DIC) occurs as a complication of diseases and conditions that accelerate clotting. This accelerated clotting process causes small blood vessel occlusion, organ necrosis, depletion of circulating clotting factors and platelets, and activation of the fibrinolytic system—which, in turn, can provoke severe hemorrhage.
Clotting in the microcirculation usually affects the kidneys and extremities but may occur in the brain, lungs, pituitary and adrenal glands, and GI mucosa. Other conditions, such as vitamin K deficiency, hepatic disease, and anticoagulant therapy, may cause a similar hemorrhage.
DIC is generally an acute condition but may be chronic in cancer patients. The prognosis depends on early detection and treatment, the severity of the hemorrhage, and treatment of the underlying disease or condition.

Etiology
DIC may result from:

• infection (the most common cause of DIC), including gram-negative or gram-positive septicemia; viral, fungal, or rickettsial infection; and protozoal infection (falciparum malaria)
• obstetric complications, such as abruptio placentae, amniotic fluid embolism, and retained dead fetus
• neoplastic disease, including acute leukemia and metastatic carcinoma
• disorders that produce necrosis, such as extensive burns and trauma, brain tissue destruction, transplant rejection, and hepatic necrosis.

Other causes include heatstroke, shock, poisonous snakebite, cirrhosis, fat embolism, incompatible blood transfusion, cardiac arrest, surgery necessitating cardiopulmonary bypass, giant hemangioma, severe venous thrombosis, and purpura fulminans.
It isn’t clear why such disorders lead to DIC; nor is it certain that they lead to it through a common mechanism. In many patients, the triggering mechanisms may be the entrance of foreign protein into the circulation and vascular endothelial injury.

Brief Summary of Multiple myeloma

Multiple myeloma is also known as malignant plasmacytoma, plasma cell myeloma, and myelomatosis. It’s a disseminated neoplasm of marrow plasma cells that infiltrates bone to produce osteolytic lesions throughout the skeleton (flat bones, vertebrae, skull, pelvis, ribs); in late stages, it infiltrates the body organs (liver, spleen, lymph nodes, lungs, adrenal glands, kidneys, skin, GI tract). Multiple myeloma strikes mostly men older than age 40.
The prognosis is usually poor because the disease is commonly diagnosed after it has already infiltrated the vertebrae, pelvis, skull, ribs, clavicles, and sternum. By then, skeletal destruction is widespread and, without treatment, leads to vertebral collapse. Early diagnosis and treatment prolong the lives of many patients by 3 to 5 years. Death usually follows complications, such as infection, renal failure, hematologic disorders, fractures, hypercalcemia, hyperuricemia, or dehydration.

Pathophysiology
Multiple myeloma is characterized by excessive growth and malformation of plasma cells in bone marrow. The growth of these extra cells interferes with the production of red blood cells, white blood cells, and platelets, resulting in anemia, susceptibility to infection, and increased tendency toward bleeding. As the cancer cells grow and expand, pain and destruction of bone occurs.

Signs and symptoms
The earliest symptom of multiple myeloma is usually back pain. This disease should be considered in diagnosis or treatment of elderly patients with new onset of lower back pain. Arthritic symptoms may also occur: achiness, joint swelling, and tenderness, possibly from vertebral compression. Other effects include fever, malaise, slight evidence of peripheral neuropathy (such as peripheral paresthesia), pathologic fractures, and easy bruising.

As multiple myeloma progresses, symptoms of vertebral compression may become acute, accompanied by anemia, weight loss, thoracic deformities (ballooning), and loss of body height due to vertebral collapse.

Introduction to Pernicious Anemia

Pernicious anemia is a decrease in red blood cells that occurs due to impaired absorption of vitamin B-12 because of a lack of intrinsic factor (IF) in gastric secretions.

It occurs as a relatively common adult form of anemia that is associated with gastric atrophy and a loss of IF production and as a rare congenital autosomal recessive form in which IF production is lacking without gastric atrophy.

By definition, pernicious anemia refers specifically to vitamin B-12 deficiency resulting from a lack of production of IF in the stomach.

Causes: Common causes of pernicious anemia include:

• Weakened stomach lining (atrophic gastritis)
• An autoimmune condition in which the body’s immune system attacks intrinsic factor protein or the cells that make it.

Very rarely, pernicious anemia is passed down through families. This is called congenital pernicious anemia. Babies with this type of anemia do not make enough intrinsic factor or cannot properly absorb vitamin 12 in the small intestine.

Pathology
Vitamin B12 cannot be produced by the human body, and must be obtained from the diet. Normally, dietary B12 is absorbed by the body in the small bowel only when it is bound by the intrinsic factor (IF) produced by parietal cells of the gastric mucosa. Pernicious anemia is thought to occur when the body’s immune system mistakenly targets the IF, with a loss of parietal cells. Insufficient IF results in insufficient absorption of the vitamin. Although the normal body stores three to five years’ worth of B12 in the liver, the usually undetected autoimmune activity in one’s gut over a prolonged period of time leads to B12 depletion and the resulting anemia. Inhibition of DNA synthesis in red blood cells results in the formation of large, fragile megaloblastic erythrocytes.

Introduction to Von Willebrand’s Disease

Von Willebrand’s disease is the most common congenital disorder of hemostasis. It is transmitted in an autosomal dominant pattern. It is characterized by deficient or defective von willebrand factor. Von willebrand factor plays a role in platelet adhesion to damaged subendothelium as well as stabilizing factor VIII in plasma.

Clinical Manifestations

• It can affect both males and females.
• Most bleeding is mucosal ( epistaxis, gingival bleeding, menorrhagia and GI bleeding ).
• Bleeding follows minor trauma or surgery.
• Aspirin increases bleeding while pregnancy and estrogen use decreases bleeding.

Investigations

• Bleeding time : Increased
• PT : normal
• APTT : raised
• Factor VIII : low
• vWF : low

In von willebrand’s disease bleeding time is prolonged while in Hemophilia bleeding time is normal.

An Approach To Patient With Bleeding

When ever a patient presents with the main complaint of bleeding there are three set of questions that need to be answered ;

1. Is There an Emergency?
A condition that may need and immediate resuscitation or help by a senior. The patient may seem to faint or go into shock. check the blood pressure for hypotension. Consider any signs of CNS bleeding like meningism as it is also an emergency. Also consider an underlying condition in which an apparently minor bleed may evolve into a catastrophic event like bleeding in pregnancy or the puerperium.

2. Why Is the Patient Bleeding?
It is important for a physician taking care of a patient with bleeding to think that is the bleeding with which the patient has presented is normal given the circumstances for example surgery, trauma, postpartum etc or that there is some other reason like bleeding disorder, drugs, liver disease or sepsis that is leading to the problem.

3. What is the mechanism of bleeding If it is a case of bleeding disorder?
To help find the answer some diagnostic tests need to be done like full blood count, coagulation studies, D-dimers, bleeding time etc.

Management: