Myths and Facts About Hemophilia

By Dr. Sanjay Gupta

For people with the bleeding disorder, it's a condition that 'deserves more awareness.' 

Hemophilia is a bleeding disorder that affects an estimated 20,000 people in the United States.

It’s a relatively rare condition, but one that has serious, even life-threatening implications for people like Rich Pezzillo.

Pezzillo, 29, was diagnosed with moderate hemophilia when he was 4 years old. One of his two brothers also has it, as did their grandfather. People with the condition are missing or have low levels of clotting factors — proteins that help blood clot.

The two most common forms of hemophilia are type A, which is caused by a lack of clotting factor VIII, and type B, which is caused by lack of clotting factor IX. The disorder usually occurs in males, though women can carry the mutant gene that causes it. Pezzillo’s mother is a carrier.

“You only need about five percent of clotting factor to function normally,” says Michael H. Bar, MD, a hematology oncologist at Stamford Hospital in Connecticut. “People with anything greater than five percent usually don’t have the spontaneous bleeding that severe hemophiliacs do and only notice it if they have a trauma.” People with severe hemophilia have less than one percent of clotting factor.

“A person with hemophilia bleeds longer, not faster,” Pezzillo says. "Many think that someone with hemophilia can die from a paper cut. That's just not true. In fact, the bigger problems are actually with internal bleeding,” which can damage tissues and organs. Pezzillo’s brother Anthony was diagnosed with hemophilia after he had his tonsils removed and suffered extreme bleeding. That’s when the rest of the family was tested, and Rich was diagnosed.

Pezzillo, who grew up in Rhode Island but now lives in Washington, D.C., remembers that he bruised easily as a child. When he was 18, after having his wisdom teeth removed, Pezzillo’s gums began to bleed. Stitches weren’t enough to stop the bleeding, so he was admitted to the hospital and given more than 40,000 units of clotting factor — a treatment known as replacement therapy.

While in college, Pezzillo developed spontaneous bleeds in his right thigh and left hip. Joint bleeds can cause pain and chronic swelling, and sometimes require joint replacement surgery.

Pezzillo then developed one of the most serious complications of hemophilia. In roughly 20 percent of hemophilia cases, patients’ immune systems will reject the clotting factor and produce antibodies, known as inhibitors, to fight it.

“Because the clotting factors are made from artificial sources and aren’t quite human, certain patients will have their immune system see them as foreign and attack,” Dr. Bar says. As a result, the clotting factor doesn’t work.

Treatment for people with inhibitors may require higher doses of clotting factor or special blood products known as bypassing agents.

Pezzillo now treats his hemophilia prophylactically, injecting himself with clotting factor regularly. It’s costly and time consuming, but it allows him to remain active. Pezzillo, who works for the Hemophilia Federation of America, has run multiple half-marathons and one full marathon.

“People don’t have to be tethered to the hospital anymore,” he says. “But it’s still a disease a lot of people don’t know about, and it deserves more awareness from both inside and outside the medical community.”

 source:http://www.everydayhealth.com/news/myths-facts-hemophilia/

Rare Case of Pseudotumor in non-Hemophiliac Patient Reported

by Malika Ammam, PhD

 

Researchers at the Mayo Clinic Arizona have reported a third rare case of hemophilic pseudotumor (HP) identified in a non-hemophiliac patient.

Findings from the investigation, “Hemophilic pseudotumor in a non-hemophilic patient treated with a hybrid procedure of preoperative embolization of the feeding arteries followed by surgical resection—A case report,” were published in the International Journal of Surgery Case Reports.

HP is a rare complication that occurs in 1 to 2 percent of patients with hemophilia A and B — two bleeding conditions caused by deficient clotting proteins (factor VIII in hemophilia A and factor IX in hemophilia B).

Hemophilic pseudotumor is caused by the recurrent episodic and intermittent bleeding into soft tissue and osseous regions, which alters and destroys nearby tissues. This makes HP a challenge to diagnose, requiring both advanced methodologies and a high index of clinical suspicion, particularly in non-hemophilic patients.

In this study, the researchers identified a new and extremely rare HP case in a patient without hemophilia — an infrequently observed event. A 46-year-old man with a history of Noonan’s syndrome, a disease characterized by abnormal facial features, heart defects, short stature, bleeding issues and skeletal abnormalities arrived at the clinic. The man, who had surgically corrected congenital heart disease, came in with back pain and left-sided iliopsoas mass associated radiculopathy.

The patient presented no history of trauma, received no anti-coagulation treatments, and showed no abnormalities in levels of factors VIII, IX and XI to suspect the presence of hemophilia A or B. However, his open biopsy results were consistent with HP, which the researchers believe was caused by his underlying bleeding problems.

The patient was treated using a hybrid procedure of preoperative embolization followed by surgical debridement and resection, with positive outcomes.

“To the best of our knowledge, this report represents one of three cases in the literature of hemophilic pseudotumor in a non-hemophiliac patient. It highlights the diagnostic and therapeutic challenges associated with hemophilic pseudotumors, and raises the question as to whether our patient’s unspecified bleeding diathesis put him at increased risk. This case was managed with a hybrid procedure of coil embolization and surgical resection, with excellent results,” the authors wrote.

 source: http://hemophilianewstoday.com/2016/09/19/researchers-report-rare-case-pseudotumor-non-hemophiliac-patient/

New Approach Seen to Identify Likely Carriers of Hemophilia A

by Özge Özkaya, PhD

Chinese researchers have identified a new and simple method to identify women who may be carriers of the gene that causes hemophilia A. Being able to diagnose a female carrier means that better genetic counseling can be offered to families, helping them to make informed decisions about family planning.

The study, “Evaluation of factor VIII polymorphic short tandem repeat markers in linkage analysis for carrier diagnosis of hemophilia A,” was published in the journal Biomedical Reports.

Hemophilia A is caused by mutations in a gene called factor VIII that is situated on the X-chromosome. These mutations result in an essential blood-clotting protein to be defective or completely absent, causing increased bleeding.

Due to the complexity of the FVIII gene, it is difficult to recognize the disease-causing mutation with simple genetic tests.

Researchers led by Dr. F. Zheng from the Center for Gene Diagnosis at Zhongnan Hospital, Wuhan University, analyzed two generations of a Chinese family, where the son had hemophilia A, the father was healthy, the mother was a carrier, and the daughter was a suspected carrier of hemophilia A.

They used a technique called rapid multifluorescent polymerase chain reaction (PCR), and a seven short tandem repeat (STR) markers found inside and outside the factor VIII gene, to conduct a linkage analysis of the family, and determine whether or not the girl was a carrier.

Linkage analysis is an indirect method used to identify the probability of a faulty gene being passed to the next generation. Genes tend to be passed on together with other DNA sequences or markers that are found in close physical proximity to them. Therefore, analyzing the presence of such markers in a member of a family can help predict whether that family member has also inherited the faulty gene.

STRs are short repetitive sequences of about two to five DNA letters that are repeated many times in a head to tail manner. They are commonly used as genetic markers to do linkage analysis.

Results showed that for the seven STR markers, the haplotype (or group of genes) in the son and in the mother were identical. The sister carried the same haplotype as her brother, which came from the mother.

The researchers concluded that the STR markers used in this study were informative for linkage analysis, could differentiate pathogenic and healthy haplotypes among the family members, and identify the sister as a potential carrier of hemophilia A.

source: http://hemophilianewstoday.com/2016/09/16/new-approach-identifies-likely-carriers-of-hemophilia-a-in-family/

Doctors Simultaneously Treat Patient’s Acquired Hemophilia A and Prostate Cancer

by Özge Özkaya, PhD

Researchers from San Joaquin General Hospital in California reported the case of a 66 year-old man who was simultaneously treated for acquired hemophilia A and prostate cancer.

“To our knowledge, this is the first reported case of prostate cancer diagnosed and treated simultaneously with acquired hemophilia A resulting in a favorable patient outcome,” Dr. Chirag Sheth and colleagues wrote.

The report, “Life-threatening hemorrhage from acquired hemophilia A as a presenting manifestation of prostate cancer,” was published in the Journal of Community Hospital Internal Medicine Perspectives.

The patient came to the hospital because of pain and swelling in his right thigh and an inability to walk for one month. He was diagnosed with hematoma (or abnormal collection of blood outside the blood vessels) in his right leg, which was removed by surgery.

However, following the operation, the patient started bleeding excessively and required an emergency blood transfusion.

On further analysis, researchers saw that the level of factor VIII inhibitors in his blood was very high and the factor VIII activity was less than 1 percent of normal. He was diagnosed with acquired factor VIII deficiency, also called acquired hemophilia A. It’s a very rare condition characterized by the acquisition of autoantibodies against factor VIII, an essential blood clotting protein, which leads to a predisposition to the formation of hematomas. The condition is associated with autoimmune diseases, pregnancy, giving birth, drugs, and cancer.

Once it was established that the patient had acquired hemophilia A, he was given drugs to block the production of factor VIII inhibitors.

Further investigations to determine the underlying cause of his condition revealed significantly high prostate-specific antigen in his blood, which led the scientists to diagnose him with locally advanced prostate cancer.
Based on his high risk of bleeding and his overall critical condition, the patient was given only hormonal therapy to treat the cancer.

After a 35-day period of hospitalization, and a two-day intervention against minor bleeding, the patient was discharged.

At the three months follow-up, no more bleeding episodes were recorded, there were no factor VIII inhibitors in his blood, and factor VIII activity was increased to 170 percent.

According to the researchers, “the patient continues to remain asymptomatic with regular follow-up in our outpatient hematology and oncology clinic.”

The authors concluded that this case demonstrates the importance of recording episodes such as sudden onset of bleeding in patients who had no prior personal or family history of similar bleeding episodes.
They said this patient’s case illustrates that simultaneous treatment of underlying cause (in this case prostate cancer) along with immunosuppressive therapy can result in a favorable outcome in acquired hemophilia A.

source: http://hemophilianewstoday.com/2016/09/14/simultaneous-treatment-acquired-hemophilia-prostate-cancer/

Knee Problems in Hemophilia Best Treated by Factor Replacement Therapy, Paper Says

by Alisa Woods, PhD

Joint problems caused by chronic bleeding often trouble people with hemophilia, especially in the knees, ankles, and elbows. A paper by scientists in Spain and the U.S. reviewed existing literature on knee treatments for people with this disease, focusing on best current practices — including a preventive, if inconveniently lifelong, therapy — and future treatment directions.

The article, “Orthopedic disorders of the knee in hemophilia: A current concept review,” was published in the World Journal of Orthopedics.

Hemophilia’s two forms are caused by deficiencies in clotting proteins,  factor VIII (FVIII) for hemophilia A and  factor IX (FIX) for hemophilia B. According to a recent study reported in Hemophilia News Today, these problems may be more severe in people with hemophilia A than those with hemophilia B.

The study’s lead authors, E. Carlos Rodriguez-Merchan of the Department of Orthopedic Surgery, La Paz University Hospital-IdiPaz, Madrid, and Leonard A. Valentino of Rush University Medical Center, Chicago, report that factor replacement therapy (FRT) is the optimal approach for preventing knee and other joint problems (known as hemophilic arthropathy), through infusions to replace the deficient protein. But use of FRT therapy is  lifelong, making adherence a challenge, and breakthrough bleeding is common. Surgery can correct damage to the knee, but is difficult in people with this bleeding disorder.

If FRT therapy is insufficient, hemophilic synovitis can develop, a condition affecting the synovial membrane that lines joints such as the knee. Rodriguez-Merchan and Valentino recommend radiosynovectomy as the best way to reduce bleeding in people with this condition. This involves injections of radioactive nucleotides into the knee. The method can replace surgical synovectomy (the removal of the synovial membrane).

The researchers recommend that these knee surgeries be performed in specialized hospitals, with experienced teams of healthcare providers, to minimize the heightened risk of bleeding and infection.

“Until we are able to prevent orthopedic problems of the knee” in people with hemophilia, we “will have to continue performing orthopedic procedures (arthrocentesis, RS [radiosynovectomy], arthroscopic synovectomy, hamstring release, arthroscopic debridement, alignment osteotomy, and total knee arthroplasty)” to improve patients’ quality of life, the authors wrote.

But, they conclude: “The best treatment …  is primary prophylaxis [FRT therapy] replacing the deficient clotting factor with early institution of regular injections of concentrates of factor VIII or IX. In this way, not only is bleeding into the joints prevented but also the development of synovitis and articular degeneration.”

Alisa G. Woods, Ph.D., MS is an Assistant Professor of the Biochemistry & Proteomics Group in the Department of Chemistry & Biomolecular Science at Clarkson University in Potsdam, NY.

 source: http://hemophilianewstoday.com/2016/06/27/article-examines-knee-problems-in-hemophilia/

Boy with Hemophilia A Undergoes Successful Stem Cell Transplant, Researchers Report

by Margarida Azevedo

A number of clinical studies have reported that bone marrow-derived cells contribute to the production of clotting factor VIII (FVIII), the molecule linked to hemophilia A. Because the current treatment for this bleeding disorder is associated with some disadvantages and risk, hematopoietic stem cell transplant (HSCT) has become an emerging therapy approach for these patients.

In this study, researchers describe the case of a 4-year-old boy with mild congenital hemophilia A who underwent a successful HSCT.

The research paper, “Successful Allogenic Haematopoietic Stem Cell Transplantation in a Boy with Hemophilia A and MDS-RAEB,” was published in Klinische Padiatrie.

Treatments to manage hemophilia A, a disease caused by a deficiency of FVIII, has led to an increase in patients’ life expectancy. But risks exist, including developing leukemia or other neoplasia later in life, along with elevated incidences of diseases like HIV and hepatitis C.

This may indicate that more patients with hemophilia A and other bleeding disorders may need HSCT. While the liver is the main production site of FVIII, some studies have also reported a contribution of bone-marrow derived cells to FVIII-production, but little is known about the clinical relevance of this fact.

In this study, researchers said the boy who underwent allogeneic (from a donor) HSCT was first assessed at age 2, when he presented with easy bruising, prolonged partial thromboplastin time (PTT) — a test used to assess how long the blood takes to clot — and marked thrombocytopenia, the clinical term for platelet deficiency.

However, due to an unremarkable bone marrow analysis and a recent upper airway infection, the symptoms were attributed to another condition and ultimately resolved.

At age 4, the boy presented again with increasing bleeding symptoms and prolonged PTT and he was eventually diagnosed with mild hemophilia A with a residual FVIII-activity of 18 percent in absence of FVIII-inhibitors. Additional examinations revealed MDS-RAEB (myelodysplastic syndrome-refractory anemia with excess blasts). MDS is considered a type of cancer and occurs when the blood-forming cells in the bone marrow are damaged, which leads to low levels of any type of blood cell.

After HSCT, the FVIII activity spontaneously increased to a maximal level of 45 percent, remained elevated for four weeks, but ultimately declined to pre-HSCT levels two months later. The child’s recovery to the procedure went well, with no associated toxicity or immune system rejection.

“At the last follow-up the patient was well and in stable hematological remission. F-VIII-activity was 19.6 percent and he did not present any bleeding symptoms,” the researchers wrote.

Despite limited resource studies evaluating HSCT for hemophilia A, the researchers concluded that the procedure is not clinically relevant in terms of FVIII production.

“Although the experience is very limited, current clinical studies do not provide evidence for a relevant contribution of donor bone marrow-derived progenitors to FVIII-synthesis,” they wrote.

source: http://hemophilianewstoday.com/2016/09/01/successful-allogenic-stem-cell-transplant-boy-hemophilia-a/ 

Brain Hemorrhage in Boy with Hemophilia Treated with Transfusions

BY Margarida Azevedo 

Researchers in India recently reported the case of child with hemophilia and traumatic intracerebellar hemorrhage, who was successfully treated with transfusions of plasma. They recommend a conservative approach as a first line of treatment, before more invasive alternatives such as surgery.

The case report, “Intracerebellar haemorrage in a haemophilia child,” was published in the Asian Journal of Neurosurgery
 .
Hemophilia A is caused by deficiency of clotting factor VIII, and its treatment is usually managed with factor replacement products and medications. Access to these products, however, can be difficult for patients in developing nations.

A 12-year-old boy, with a history of transient loss of consciousness and vomiting, sustained a head injury in a fall, and was taken to SCB Medical College and Hospital, in Cuttack, Odisha. Through a computed tomography (CT) scan, physicians identified a well-defined lesion in the intracranial cavity of the boy’s brain. As acute intracerebellar bleeding was suspected, the child was advised to see a neurosurgeon. But his condition was stable, and his parents decided to differ.  Some six weeks after the incident, however, the boy returned to the hospital with symptoms of headache, intermittent vomiting, and an unsteady gait. Magnetic resonance imaging of brain revealed mid-posterior cerebellar, sub-acute, intracerebellar bleeding.

The boy’s coagulation profile was suggestive of moderately severe hemophilia. He was treated with six units of fresh frozen plasma and intravenous tranexamic acid, a medication used to control unwanted bleeding. This treatment led to clinical improvement  and, eventually, the hematoma spontaneously resolved. Such results indicate that early detection and correction of factor levels when intracranial bleeding occurs could prevent possible life-threatening complications.

“Choosing safe sports is vital for children with hemophilia. In case of traumatic intracranial bleed, prompt diagnosis and conservative approach through procoagulant transfusion and intravenous fibrinolysis inhibitors should be tried as first line of management. Before daring for surgery, sufficient amount of factor replacement should be kept available,” the researchers concluded.

 source: http://hemophilianewstoday.com/2016/08/30/brain-hemorrhage-in-hemophilia-boy-successfully-treated-with-transfusions/