Rising incidence of hematological disorders and surgical procedures has led to growth in demand for platelets and plasma products for efficient treatment and improvement in survival rates. While the demand for blood is increasing, blood stocks are barely adequate to meet basic requirements. Despite substantial development in the field of medicine, effective substitutes of blood products have not yet been developed. In the absence of such substitutes, blood remains the mainstay of treatment for a wide range of medical condition, and therefore well-organized and effective blood transfusion service is vital for the healthcare delivery system.

Nowadays, most blood banks split the whole blood into its components to prevent transfusion associated circulatory overload (TACO) contributed by transfusion of extra plasma. This restriction makes the usage of whole blood transfusion less common among doctors who are insisting on transfusing blood components for treatment of diseases. This increasing preference toward usage of blood components will result in increased demand of advanced blood component separating technologies in the near future.

Researchers, healthcare practitioners, and manufacturers worldwide are introducing solutions that demand minimum human intervention and allow agility in the separation process. Companies are engaged in the development of advanced instruments for the easy preparation of blood components. With the development of high-speed technology for separating blood components, the market is expected to reach new heights.

Global Market

The global apheresis equipment market was valued at USD 1.89 billion in 2016 and is projected to grow at a CAGR of 11.4 percent from 2017 to 2024, predicts Global Market Insights. Untapped emerging regions showcase new growth opportunities for this market. However, the growth of the market is restrained by the lack of awareness about apheresis, scarcity of qualified donors, and the high cost of these equipment and procedures.

Centrifugation, surface marker, and filtration-based technologies are majorly adopted to separate the various blood components. In 2016, the centrifugation-based separation accounted for the largest share of the global market primarily due to its wide usage among end users.

Disposable apheresis kits accounted for the largest market share in 2016, and will be the fastest growing segment by surpassing USD 2944 million by 2024 due to its growing acceptance and relatively lower prices. Apheresis equipment which includes centrifugation is expected to witness robust 17.1 percent CAGR from 2017 to 2024 due to the increasing need for automated component-separation equipment.

The market is oligopolistic in nature and is marked by an extensive presence of mergers and acquisitions. New product developments, acquisitions, and strategic alliances are some major sustainability strategies adopted by the industry players. Some of the key players in this market are Haemonetics Corporation, Fresenius Medical Care, Terumo BCT Inc., Asahi Kasei Medical Co. Ltd., Kawasumi Laboratories Inc., Cerus Corporation, B. Braun Melsungen AG, HemaCare Corporation, Kaneka Corporation, and Nikkiso Co. Ltd.

Strategies promoting faster distribution and development of efficient supply chain are being incorporated by the players. For instance, in October 2016, Cerus Corporation entered into a distribution agreement with Hemolife Fundacin Banco Nacional de Sangre and in December 2016, Fresenius Kabi USA and Terumo Cardiovascular Group entered into a five-year distribution agreement.

Blood Bank Centrifuges

The blood banks are dependent on consistent and accurate centrifuge operation in order to separate serum/plasma from cellular components. Plasma separation from raw whole blood is usually required for blood-based clinical diagnostics. Centrifuges, working on the principle of sedimentation, are being used widely for the separation of blood cells based on size and density into more manageable cell populations. Increasing government initiatives for R&D and increasing advancement in clinical and medical fields to develop access to better healthcare are playing a key role in the development of new-generation centrifuges. The speed and dependency that modern centrifuges bring to the blood banks make them an invaluable technology to integrate automation.

Technology Trends

The safety and efficiency of modern clinical centrifuges continues to improve with many manufacturers and suppliers seeking to reduce the time it takes for the equipment to reach the designated speed as well as reduce the time required to stop the centrifugation process. Moreover, with the increasing requirement of centrifuges, companies are introducing systems with new innovative products having advanced features. These advanced centrifuge systems or the new-generation centrifuges tend to overcome the problems related to the speed, efficiency, and volume faced when using the conventional centrifuge system.

Continuous flow centrifuges. They function at relatively higher speeds as compared to the normal centrifuges. Continuous flow of liquid during centrifugation process saves time by eliminating several loading/unloading and accelerating/decelerating steps. Continuous flow centrifuges are also known for separating larger volumes compared to conventional methods. They have features such microprocessors to achieve above parameters very precisely, frequency-driven motor for smooth operation, and internal memory to store programs which helps in getting quality results with a single button operation.

Ultracentrifuges. Modern ultracentrifuges accelerate at a speed of more than 50,000 revolutions per minute (rpm), thereby generating very high relative centrifugal force (RCF). Efficiency and range of activities of these latest equipment reflect the technological progress during the past 3–4 decades with the upcoming microchip technology, the construction of new heavy-duty drive systems, the installation of a sophisticated control equipment, and last but not least the access to the novel carbon-fiber material in the design of rotors. While the alignic floor-standing ultracentrifuge has been revolutionized by these groundbreaking changes to its design, with the benchtop version, a novel model matching the demands on flexibility and versatility of experimental working has been launched in the meantime.

Next-generation centrifuges. The next-generation system includes advanced features such as automatic electric brakes, solid-state speed control, electronic tachometer, and safety cut off switch to stop the system if the lid is open. They are microprocessor controlled smart centrifuges, which provide high efficiency with more memory storage. These centrifuges provide precise temperature control, wide range of RCF, acceleration, and time. These centrifuges also allow network and PC connectivity which helps in data management.

Blood Cell Separators

Blood plays an important role in homeostatic regulation with each of its cellular components having important therapeutic and diagnostic uses. Therefore, separation and sorting of blood cells has been of great interest to clinicians and therapeutic researchers. Since the separation of red and white blood cells was first reported in 1974, the technology has become fundamental to the biomedical sciences. Functional and phenotypic analyses of blood cells provide useful clinical information for disease diagnosis and treatment.

Government Initiatives

While the health sector in India has made outstanding accomplishments in the past few decades, it has not reciprocated sufficiently to fulfill the country's objective on blood-transfusion facilities. Although National Blood Policy of India acknowledges this grave situation and has proposed an increase in its blood storage facility, its translation into reality is still a distant dream. Therefore, there is the need to transform the present state-of-affairs to the necessary state-of-the-art in terms of blood storage facilities.

To strengthen the blood transfusion services, the Ministry of Health and Family Welfare (MoHFW) under its Metro Blood Bank Project will set up state-of-the-art centers of excellence in transfusion medicine in the four Metro cities of Delhi, Mumbai, Chennai, and Kolkata. These centers are high-volume blood-collection centers where there is state-of-the-art technology in transfusion medicine for component separation, processing of blood, and quality systems. Facilities for screening of collected blood by nucleic acid testing (NAT) would be made available at these centers and also extended to the other blood banks of the state.

National Blood Transfusion Council under National AIDS Control Organization (NACO) will be the implementing division of the Ministry for this project. Approval of Union Minister of Health and Family Welfare has been accorded for the first phase, wherein these facilities are to come up in Chennai and Kolkata.

Taking this forward, a memorandum of understanding (MoU) was signed by MoHFW with Government of Tamil Nadu in June 2017 and with Government of West Bengal in July 2017 to formalize the central government support to set up and run these centers in the respective states. The land for this initiative will be provided free of cost by the State government. Central government has approved an outlay of approximately 200 crore per center for this important initiative.

Despite the current advances in healthcare delivery, access to safe blood and blood products and their judicious use remains a big challenge. Rational use of blood also needs to be ensured to enhance utilization, as one unit of blood can benefit more than one beneficiary through separation into red cells, plasma, and platelets.

Technology Trends

Based on the variety of principles used, current existing cell isolation technologies can be alignified into two groups. The first group is based on physical properties like size, density, electric changes, and deformability, with methods including density gradient centrifugation. The second group is based on cellular biological characteristics, comprising affinity methods, such as affinity solid matrix (beads, plates, and fibers), fluorescence-activated cell sorting (FACS), and magnetic-activated cell sorting (MACS), which are based upon biological protein expression properties.

FACS and MACS. FACS can sort up to 50,000 cells per second, with higher rates achievable at the cost of purity. Despite various positive advances and being the most user-friendly technologies, these methods have drawbacks. The use of fluorescent chemicals or antibodies to indicate the target population makes them expensive. Cell losses in FACS and MACS can exceed half the population, particularly at high sorting rates.

DACS. An emerging alternative separation technology to FACS and MACS is dielectrophoresis (DEP) that can be used both to characterize and separate cells according to passive electrical properties. The DEP-based cell-separation (DACS) has a capacity and throughput comparable to the fastest MACS and FACS, requires no chemical labels, has significantly lower cell loss, and significantly lower capital and running costs. Furthermore, the self-contained and low-cost nature of the separator equipment means that it has potential application in low-contamination applications such as cell therapies, where good manufacturing practice compatibility is of paramount importance.

Microfluidics. Recent advances in cell sorting aim to develop novel methods that are sensitive to various mechanical properties of cells. As microfluidics involves fluid manipulation at the microscale level, it has the potential for achieving high-resolution separation and sorting of blood cells down to a single-cell level. These lab-on-a-chip technologies provide a promising alternative to the current gold-standard cell-sorting approaches. Microfluidic devices have multiple advantages over conventional approaches including reduced manufacturing costs, a smaller sample volume requirement, and the ability to sort cells based on their intrinsic properties, leading to an increased automation of the sorting process.

Road Ahead

A 2016 assessment of Indian blood banks supported by NACO shows that 87 districts have no blood banks.Among the 1000 odd public blood banks, only 74 percent had basic functionality and just 31 percent had advanced blood-separation component units. Most government-owned blood banks do not have fractionalization facility that can process the blood and break it into components. Lack of blood, plasma, or platelets often becomes the cause for maternal mortality and deaths in accident cases.

Considering the deleterious effect of poor quality practices on patient care, it is imperative that specific programs and strategies to improve quality systems are developed and implemented across the country. In order to cater to healthcare needs of its ever growing population, improve the quality of life for its citizens, and fight against various seasonal outbreaks of dengue, India would need several blood component separation units in the near future. There exists tremendous scope for manufacturers to establish and expand themselves in the country by producing world align equipment.

Dr Anil Khetarpal

Second Opinion,

Essential Blood Component Separation Devices.

The modern day transfusion medicine has the ability to provide transfusion products specific to the patient's need which greatly improves treatment outcomes and maximizes the donor resources. Separation of whole blood into its constituents allows optimal survival of each component. This ability to transform whole blood into various components relies heavily on good centrifuges and component separators.

Blood Bank Centrifuges

These are the backbone of a blood-banking lab. It is vital that the centrifuges should be reliable and able to provide fully reproducible and traceable data with every spin. With downstream patient-safety implications, separation of whole blood into its components needs to be tightly regulated and should be in compliance with good manufacturing practices (GMP). Following are the desired qualities for a good centrifuge:

  • High product yield with highest spin for separation
  • Short processing time
  • To provide lowest possible speed for least trauma to cellular integrity
  • Maintain constant temperature over a wide range to suit varied temperature needs of each component
  • Processing of large volumes
  • Reproducible and accurate centrifugation
  • Safe operation with armored rotor chamber and lid-lock system

Blood Cell Separators

These are required to transfer different layers of the components (red cells, platelets, plasma) to the satellite bags within the closed systems, in a manner designed to optimize the harvest of the intended component while minimizing the carry-over of other component fractions. Following are the desired qualities for a good cell separator:

  • Should allow easy follow-up of each step of the separation process; component flow, component weights, clamp positions, sealing functions, and flow
  • Should have a provision for procedures like air removal of filtered whole blood and aliquoting
  • Safe press system to mitigate injuries during processing – operator friendly
  • Should provide high stability of layers during extraction and standardized small rest volume

These machines have made the component therapy a reliable and feasible reality, thus optimizing the patient care and blood resource usability.

Dr Anil Khetarpal
Chairperson,
Department of Transfusion Medicine,
Artemis Hospitals, Gurgaon

Dr Suman Hegde

Second Opinion

Progressing Technology

Blood Cell Separators

Earlier than 1960s, there used to be a laborious procedure to remove white blood cells (WBCs) from a leukemic patient wherein they would remove two units (450 ml) of blood, spin them in a bucket centrifuge, express the plasma into a satellite bag, WBCs into another satellite bag; the packed cells and plasma would be then recombined and administered back to the patient. Present breakthrough inventions pave way for simple and very rapid collection of RBCs, granulocytes, mononuclear cells, platelets, plasma, peripheral blood stem cells, and bone marrow stem cells with high resolution. The collection can be made independent of other blood components. For instance, only RBCs, or only platelets, or if desired all blood components can be harvested at the same time in separate containers causing minimal damage to blood components with continuous blood flow through. The present day devices have latest microprocessors and sensor technologies based on the immune magnetic cell-separation principle. Here cells are magnetically labelled and separated by positive and negative selection. This minimizes sample handling, eliminates cross-contamination, and reduces hands on time. Fully automated versions with an option of switching over to manual at any point of time are available. Compact and portable designs make them easy to transport.

Blood Bank Centrifuges

Centrifuges featuring large capacity in compact footprint, glove friendly center touch – interface, automatic door opening and closing with auto door, store lid functioning automatically with autolid are available with remote monitoring and control systems. Password protection for multiuser environment, energy savings with eco-spin wind-shielded rotors, CFC-free refrigeration system with pre cooling facility, maintenance free brushless induction motor, low-level of vibration, and noise with smooth acceleration and deceleration upgrade these centrifuges. An option to open in case of power failure, easy loading and unloading facilities make them user friendly. Acceleration and deceleration time can be set as per user requirement.Provision of ACE function that corrects for variations in acceleration, Centri-Cross function that converts existing protocols, and connectivity for protocol tracking enrich the present day centrifuges. They are designed to meet production needs. Models accommodating 6 550 ml blood bags, 8 550 ml blood bags, 12 500 ml blood bags, and 16 500 ml blood bags are at disposal in the market. They satisfy the latest global safety and compliance standards.

Dr Suman Hegde
Consultant Pathologist and Blood Bank Consultant,
PG Hospital's IMA Lifeline Blood Bank,
Karnataka

Dr S Madan Mohan

"I am working as CMO, Red Cross blood bank since 2004. During this period I have supervised more than 1300 blood donation camps. Day by day the scenario in running blood banks and conducting blood donation camps is changing very much. Nowadays it is looking like an unhealthy competition amongst blood banks. From 2004 to 2009, we used to collect 7000 to 8000 blood units per annum. 2009 onwards it has come down to 5000 blood units per annum. We started a component preparation unit in 2008. All these years we are preparing 30 percent components and 70 percent whole blood. Due to busy schedules people who are interested in blood donation are at times unable to donate. Because of above mentioned reasons and many other reasons we are unable to meet the need. Better solution for this is component preparation. In this we can go for three varieties of products, that is, packed RBC, platelets, and FFP. With this we can meet the needs of three patients, with one VBD. We can save FFP for one year. In view of the requirement, this year we are planning for 50 percent component preparation. At the same time we are putting efforts to buy one more refrigerated centrifuge (components)."

Dr S Madan Mohan
Chief Medical Officer,
Red Cross Blood Bank,
Andhra Pradesh

Dr M. Joshua Daniel

Second Opinion

Advancements and Emerging Trends

Cell-separation technologies are being increasingly used and continue to make an outstanding contribution to both technical and clinical aspects of transfusion medicine. Their applications can be either; donor-based or therapeutic- or patients-based.

In the donor-based applications the concentration is mainly toward harvest of platelets and other cellular components like peripheral blood stem cells for autologus or allogeneic bone marrow reconstitution (an alternative to bone marrow transplantation) and collection of lymphocytes for use in immune modulation cancer therapy (adoptive immunotherapy). Granulocyte concentrates are increasingly collected and used to restore host defenses in severely neutropenic patients.

In therapeutic apheresis whole blood from the patient is separated into various components (e.g., cells, plasma, proteins, antibodies, antigen–antibody complexes, lipids, etc.); the components that contribute to disease are removed while the rest are returned back to the patient. Several forms of therapeutic apheresis exist: therapeutic plasma exchange (plasma exchange; commonly known as TPE); white cell reduction (leukocytapheresis – management of acute myeloid leukemia); platelet reduction (plateletapheresis); red cell exchange (erythrocytapheresis, or RBCX – management of sickle cell disease and acute severe malaria with high parasitic index); low-density lipoprotein (LDL) apheresis; and extracorporeal photophoresis (ECP), which involves treating isolated leukocytes ex vivo with 8-methoxypsoralen and then exposing them to ultraviolet light before cells are returned to the patient.

Cell separation by counter-flow centrifugal elutriation (CCE) or free flow electrophoresis (FFE) is performed at a lower frequency compared to cell cloning and antibody-dependent, magnetic, or fluorescence-activated cell sorting. CCE and FFE have proved to be valuable tools, if homogeneous populations of normal healthy untransformed cells are required for answering scientific questions or for clinical transplantation and cells that cannot be labeled by antibodies.

Dr M. Joshua Daniel
Consultant Transfusion Medicine,
MIOT International Hospital,
Chennai

 

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